MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Journal of Peptide Science' source. Thu, 09 Feb 2012 13:38:39 +0100 http://www.medworm.com/index.php?rid=5603646&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.2391 In this study, we show that the dissolution of Aβ40, 42, and 43 in HFIP followed by drying results in highly ordered aggregates. Although α‐helical conformation is observed, it is not stable for prolonged periods. Drying after prolonged incubation of Aβ40, 42, and 43 peptides in HFIP leads to structural transition from α‐helical to β‐conformation. The peptides form short fibrous aggregates that further assemble giving rise to highly ordered ring‐like structures. Aβ16–22, a highly amyloidogenic peptide stretch from Aβ, also formed very similar rings when dissolved in HFIP and dried. HFIP could not induce α‐helical conformation in Aβ16–22, and rings were obtained from freshly dissolved peptide. The rings formed by Aβ40, 42, 43, and Aβ16–22 are composed of the pepti... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5603646 Tue, 17 Jan 2012 05:00:00 +0100 5603646 http://www.medworm.com/index.php?rid=5603645&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1438 Benzotriazole‐based coupling reagents have dominated the last two decades of solid phase peptide synthesis. However, a growing interest in synthesizing complex peptides has stimulated the search for more efficient and low‐cost coupling reagents, such as COMU which has been introduced as a nonexplosive alternative to the classic benzotriazole coupling reagents. Here, we present a comparative study of the coupling efficiency of COMU with the benzotriazole‐based HBTU and HCTU for use in in situ neutralization Boc‐SPPS. Difficult sequences, such as ACP(65–74), Jung–Redeman 10‐mer, and HIV‐1 PR(81–99), were used as model target peptides on polystyrene‐based resins, as well as polyethylene glycol‐based resins. Coupling yields obtained using fast in situ Boc‐SPPS cycles we... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5603645 Tue, 17 Jan 2012 05:00:00 +0100 5603645 http://www.medworm.com/index.php?rid=5603644&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1436 The utility of three various analytical techniques [ion chromatography (IC), capillary electrophoresis (CE) and isotachophoresis (ITP)] was tested in the determination of counter‐ions in synthetic peptides. The analyzed ions were acetates, trifluoroacetates and chlorides. IC provided the best results; CE, except limit of detection and limit of quantification, exhibited the comparable results. ITP was classified as the less useful because of the problem with the determination of the chloride ions. Nevertheless, all the three techniques were able to analyze trifluoroacetates and acetates ions with satisfactory results. Except analytical methods, three procedures using hydrochloric acid (HCl) (at two different concentrations) and acetic acid as sample solvents processed by lyophilization we... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5603644 Tue, 17 Jan 2012 05:00:00 +0100 5603644 http://www.medworm.com/index.php?rid=5603651&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1430 In contrast to the large number of sidechain protecting groups available for cysteine derivatives in solid phase peptide synthesis, there is a striking paucity of analogous selenocysteine Se‐protecting groups in the literature. However, the growing interest in selenocysteine‐containing peptides and proteins requires a corresponding increase in availability of synthetic routes into these target molecules. It therefore becomes important to design new sidechain protection strategies for selenocysteine as well as multiple and novel deprotection chemistry for their removal. In this paper, we outline the synthesis of two new Fmoc selenocysteine derivatives [Fmoc‐Sec(Meb) and Fmoc‐Sec(Bzl)] to accompany the commercially available Fmoc‐Sec(Mob) derivative and incorporate them into two mo... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5603651 Mon, 16 Jan 2012 05:00:00 +0100 5603651 http://www.medworm.com/index.php?rid=5603650&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1434 We report a series of synthetic anticancer heptapeptides (H‐KKWβ2,2WKK‐NH2) containing eight different central lipophilic β2,2‐amino acid building blocks, which have demonstrated high efficiency when used as scaffolds in small cationic antimicrobial peptides and peptidomimetics. The most potent peptides in the present study had IC50 values of 9–23 µm against human Burkitt's lymphoma and murine B‐cell lymphoma and were all nonhaemolytic (EC50 > 200 µm). The most promising peptide 10e also demonstrated low toxicity against human embryonic lung fibroblast cells and peripheral blood mononuclear cells and exceptional proteolytic stability. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.We report a series of synthetic anticancer heptapeptides (... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5603650 Mon, 16 Jan 2012 05:00:00 +0100 5603650 http://www.medworm.com/index.php?rid=5603649&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1439 Antimicrobial peptides are important effector molecules of the innate immune system. Here, we describe that peptides derived from the heparin‐binding disulfide‐constrained loop region of human ß‐amyloid precursor protein are antimicrobial. The peptides investigated were linear and cyclic forms of NWCKRGRKQCKTHPH (NWC15) as well as the cyclic form comprising the C‐terminal hydrophobic amino acid extension FVIPY (NWCKRGRKQCKTHPHFVIPY; NWC20c). Compared with the benchmark antimicrobial peptide LL‐37, these peptides efficiently killed the Gram‐negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram‐positive Staphylococcus aureus and Bacillus subtilis, and the fungi Candida albicans and Candida parapsilosis. Correspondingly, fluorescence and electron microscopy de... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5603649 Mon, 16 Jan 2012 05:00:00 +0100 5603649 http://www.medworm.com/index.php?rid=5603648&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1433 ABSTRACTThe stereocontrolled synthesis of fully protected (2S,4S,6S)‐2‐amino‐6‐hydroxy‐4‐methyl‐8‐oxodecanoic acid was accomplished using a glutamate derivative as starting material. The key steps of this stereochemical synthetic pathway involved an Evans asymmetric alkylation, a Sharpless asymmetric epoxidation, and a Grignard reaction. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.The stereocontrolled synthesis of fully protected (2S,4S,6S)‐2‐amino‐6‐hydroxy‐4‐methyl‐8‐oxodecanoic acid was accomplished using a glutamate derivative as starting material. The key steps of this stereochemical synthetic pathway involved an Evans asymmetric alkylation, a Sharpless asymmetric epoxidation, and a Grignard reaction. (Source: Journal of Pe... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5603648 Mon, 16 Jan 2012 05:00:00 +0100 5603648 http://www.medworm.com/index.php?rid=5603647&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1435 Peptide uptake by plant roots from degraded soybean‐meal products was analyzed in Brassica rapa and Solanum lycopersicum. B. rapa absorbed about 40% of the initial water volume, whereas peptide concentration was decreased by 75% after 24 h. Analysis by reversed‐phase HPLC showed that number of peptides was absorbed by the roots during soaking in degraded soybean‐meal products for 24 h. Carboxyfluorescein‐labeled root hair‐promoting peptide was synthesized, and its localization, movement, and accumulation in roots were investigated. The peptide appeared to be absorbed by root hairs and then moved to trichoblasts. Furthermore, the peptide was moved from trichoblasts to atrichoblasts after 24 h. The peptide was accumulated in epidermal cells, suggesting that the peptide may ha... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5603647 Mon, 16 Jan 2012 05:00:00 +0100 5603647 http://www.medworm.com/index.php?rid=5603643&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.2392 Histone deacetylase inhibitors (HDACIs) are a promising class of anticancer agents. To examine whether a slight change in the recognition domain could alter their inhibitory activity, we synthesized a series of cyclo(−l‐Am7(S2Py)‐Aib‐l‐Phe(n‐Me)‐d‐Pro)derivatives and evaluated their HDAC inhibitory and anticancer activities. The peptides exhibited potent HDAC inhibitory activity and inhibited three human cancer cell lines with IC50 in the micromolar range. Docking and molecular dynamics simulation were conducted to explore the interaction mechanisms of class I and II HDACs with these inhibitors. It revealed that the zinc ion in the active site coordinated five atoms of HDACs and the sulfur atom of the inhibitor. The metal binding domains of these compounds interacted with H... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5603643 Sun, 01 Jan 2012 05:00:00 +0100 5603643 http://www.medworm.com/index.php?rid=5482753&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1428 The taste of peptides is seldom one of the most relevant issues when one considers the many important biological functions of this class of molecules. However, peptides generally do have a taste, covering essentially the entire range of established taste modalities: sweet, bitter, umami, sour and salty. The last two modalities cannot be attributed to peptides as such because they are due to the presence of charged terminals and/or charged side chains, thus reflecting only the zwitterionic nature of these compounds and/or the nature of some side chains but not the electronic and/or conformational features of a specific peptide. The other three tastes, that is, sweet, umami and bitter, are represented by different families of peptides. This review describes the main peptides with a sweet, um... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5482753 Wed, 07 Dec 2011 05:00:00 +0100 5482753 http://www.medworm.com/index.php?rid=5482752&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1419 The ability to speed up conventional Fmoc solid‐phase peptide synthesis (SPPS) has many advantages including increased productivity. One way to speed up conventional Fmoc SPPS is the choice of activator. Recently, several new activators have been introduced into the market, and they were evaluated along with some older activators for their ability to synthesize a range of peptides with shorter and longer reaction times. It was found that HDMC, PyClock, COMU, HCTU, and HATU worked well at shorter reaction times (2 × 1 min), but PyOxim and TFFH only worked well at longer reaction times. The performance of PyBOP at shorter reaction times was poor only for more difficult sequences. These results are important for selecting an appropriate activator for fast SPPS applications. Copyright... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5482752 Thu, 01 Dec 2011 05:00:00 +0100 5482752 http://www.medworm.com/index.php?rid=5447391&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1426 Alpha‐helical region substitution was applied to the SIAH1 and EL5 RING fingers. The Williams–Beuren syndrome transcription factor (WSTF) PHD_SIAH1 and WSTF PHD_EL5 RING fingers were created as the artificial ubiquitin‐ligating enzyme (E3). These fingers possess E3 activities of mono‐ubiquitination and poly‐ubiquitination, respectively, with ubiquitin‐conjugating enzyme (E2)‐binding capabilities. Artificial E3s bind two zinc atoms and adopt a zinc‐dependent ordered structure and ubiquitinate upon themselves without a substrate and a tag. Ubiquitination experiments using biotinylated ubiquitin showed that the WSTF PHD_EL5 RING finger is poly‐ubiquitinated via residue Lys63 of ubiquitin. Substitution of alpha‐helical region might be applicable to various RING fingers with... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5447391 Sat, 26 Nov 2011 07:19:15 +0100 5447391 http://www.medworm.com/index.php?rid=5437072&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1418 Several polypeptides aggregate into insoluble amyloid fibrils associated with pathologies such as Alzheimer's disease, Parkinson's disease and type 2 diabetes. Understanding the structural and sequential motifs that drive fibrillisation may assist in the discovery and refinement of effective therapies. Here we investigate the effects of three predicted amyloidogenic regions on the structure of aggregates formed by medin, a poorly characterised polypeptide associated with aortic medial amyloidosis. Solid‐state NMR is used to compare the dynamics and sheet packing arrangement of the C‐terminal region encompassing residues F43GSV within full‐length medin (Med1‐50) and two shorter peptide fragments, Med30‐50 and Med42‐49, lacking specific sequences predicted to be amyloidogenic.. R... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5437072 Wed, 23 Nov 2011 06:43:44 +0100 5437072 http://www.medworm.com/index.php?rid=5417154&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1403 We report here a complete investigation of the scope and limitations of the deprotective potential of 2,2′‐dithiobis(5‐nitropyridine) (DTNP) on a selection of commercially available Cys S‐protecting groups. The gentle conditions of DTNP in a TFA solvent system show a remarkable ability to deprotect some cysteine blocking functionality traditionally removable only by more harsh or forcing conditions. Beyond illustrating the deprotective ability of this reagent cocktail within a cysteine‐containing peptide sequence, the utility of this method was further demonstrated through iterative disulfide formation in oxytocin and apamin test peptides. It is shown that this methodology has high potential as a stand‐alone cysteine deprotection technique or in further manipulation of disulfid... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5417154 Thu, 17 Nov 2011 21:24:59 +0100 5417154 http://www.medworm.com/index.php?rid=5417159&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1420 In this study, a novel [Met5]enkephalin amide (MEA) analogue [Met5]enkephalin (ME)‐semicarbazide synthesized by another laboratory in our group was assessed for its antinociceptive effects compared with ME‐ethylamide, MEA and ME, using tail flick test. To protect the administered drugs from biodegradation, rats were pretreated with peptidase inhibitors including amastatin, phosphoramidon and captopril. Then captopril (dipeptidyl carboxypeptidase‐I inhibitor) was deleted from the peptidase inhibitors' combination for evaluating in vivo resistance of the synthetic drugs to dipeptidyl carboxypeptidase‐I.According to the results, ME‐semicarbazide and MEA were resistant enough to dipeptidyl carboxypeptidase‐I to exert their strong antinociception following intrathecal administration... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5417159 Mon, 14 Nov 2011 05:00:00 +0100 5417159 http://www.medworm.com/index.php?rid=5417158&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1416 ABSTRACTAbnormal fibrillization of amyloidogenic peptides/proteins has been linked to various neurodegenerative diseases such as Alzheimer's and Parkinson's disease as well as with type‐II diabetes mellitus. The kinetics of protein fibrillization is commonly studied by using a fluorescent dye Thioflavin T (ThT) that binds to protein fibrils and exerts increased fluorescence intensity in bound state. Recently, it has been demonstrated that several low‐molecular weight compounds like Basic Blue 41, Basic Blue 12, Azure C, and Tannic acid interfere with the fluorescence of ThT bound to Alzheimers' amyloid‐β fibrils and cause false positive results during the screening of fibrillization inhibitors. In the current study, we demonstrated that the same selected substances also decrease the... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5417158 Mon, 14 Nov 2011 05:00:00 +0100 5417158 http://www.medworm.com/index.php?rid=5417157&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1425 Lantibiotics 97518 and NAI‐107, produced by the related genera Planomonospora and Microbispora respectively, are members of a family of nisin‐related compounds. They represent promising compounds to treat infections caused by multiresistant Gram‐positive pathogens. Despite their similar structure and a similar antibacterial spectrum, the two lantibiotics exhibit significant differences in their potency. To gain an insight into the structure–activity relationships, their conformational properties in solution are determined by NMR. After carrying out an NOE analysis of 2D 1H NMR spectra, high‐resolution 3D structures are determined using molecular dynamics simulations. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.High‐resolution 3D structures of two l... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5417157 Mon, 14 Nov 2011 05:00:00 +0100 5417157 http://www.medworm.com/index.php?rid=5417156&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1422 The yeast‐like algae of the genus Prototheca are ubiquitous saprophytes causing infections in immunocompromised patients and granulomatous mastitis in cattle. Few available therapies and the rapid spread of resistant strains worldwide support the need for novel drugs against protothecosis. Host defence antimicrobial peptides inactivate a wide array of pathogens and are a rich source of leads, with the advantage of being largely unaffected by microbial resistance mechanisms. Three structurally diverse bovine peptides [BMAP‐28, Bac5 and lingual antimicrobial peptide (LAP)] have thus been tested for their capacity to inactivate Prototheca spp. In minimum inhibitory concentration (MIC) assays, they were all effective in the micromolar range against clinical mastitis isolates as well as a P... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5417156 Mon, 14 Nov 2011 05:00:00 +0100 5417156 http://www.medworm.com/index.php?rid=5417155&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1421 In this study, we identify hGlyrichin as a potential human antibacterial polypeptide. The hGlyrichin polypeptide kills a variety of bacteria including the MDR bacteria methicillin‐resistant Staphylococcus aureus, MDR Pseudomonas aeruginosa, and MDR tubercle bacillus. A 19 amino acid peptide (pCM19) at positions 42–60 of hGlyrichin is crucial for its antibacterial activity. The hGlyrichin polypeptide kills bacteria through the destruction of the bacterial membrane. In addition, all peptides that are homologous to hGlyrichin have antibacterial activity and can penetrate the bacterial membrane. Importantly, hGlyrichin does not cause hemolytic side effects in vitro or in vivo. Therefore, based on the virtues of hGlyrichin, i.e., the absence of hetero‐immunological rejection and hemolytic... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5417155 Mon, 14 Nov 2011 05:00:00 +0100 5417155 http://www.medworm.com/index.php?rid=5396433&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1423 The synthesis and NMR elucidation of Ala‐Val‐Pro‐Ile and five novel peptide‐based derivatives are reported. These peptides mimic the natural second mitochondria‐derived activator of caspase (Smac) protein. Purification was achieved using preparative HPLC and the NMR elucidation of all compounds is reported for the first time. A series of overlapping signals were observed in the 1D NMR spectra thus making assignment a difficult task to undertake. The use of 2D NMR techniques with the inclusion of efficient adiabatic symmetrized ROESY proved to be an effective tool in overcoming these difficulties. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.The synthesis and NMR elucidation of Ala‐Val‐Pro‐Ile and five novel peptide‐based derivatives that mimic... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5396433 Fri, 11 Nov 2011 07:27:14 +0100 5396433 http://www.medworm.com/index.php?rid=5396434&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1429 C‐terminally modified peptides aldehyde (glycinal and alpha‐oxo aldehyde peptides) and ketone (pyruvic acid‐containing peptide) were synthesised to get new insights into the mechanism of acido‐catalysed oxime ligation. Their tetrahedral hydrated forms were investigated in solution and in the gas phase, using NMR and in‐source collision‐induced dissociation mass spectrometry, respectively, and the kinetics of the oximation reactions followed using analytical HPLC. The results obtained confirmed that the first step of the oximation reaction was the limiting step for the pyruvic acid‐containing peptides because of the steric effect and of the carbon angular strain of the ketone. The second step is the determining step for the aldehyde peptides because the basicity of the oxygen ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5396434 Mon, 07 Nov 2011 05:00:00 +0100 5396434 http://www.medworm.com/index.php?rid=5374714&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1414 Slc11a1 is an integral membrane protein with 12 putative transmembrane domains (TMDs) and functions as a pH‐coupled divalent metal cation transporter. The conservation of three negatively charged residues in the TMD3 of Slc11 protein family implies the important role of this domain in the function of the proteins. However, aggregation of the transmembrane peptide in micelles prevents structural study of the peptide in these membrane‐mimetic environments by NMR spectroscopy. Here, we characterized the structure, position, and assembly model of Slc11a1‐TMD3 (Lys128‐Ile151) in SDS micelles by the NMR study of its Leu‐substituted peptide. It was found that the two‐site substitutions of Ala for Leu residues at positions 136 and 140 of TMD3 disrupt the aggregation without altering th... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5374714 Thu, 03 Nov 2011 04:00:00 +0100 5374714 http://www.medworm.com/index.php?rid=5374713&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1427 The human ether‐à‐go‐go related gene (hERG) encodes a protein that forms a voltage‐gated potassium channel and plays an important role in the heart by controlling the rapid delayed rectifier K+ current (IKr). The S4–S5 linker was shown to be important for the gating of the hERG channel. Nuclear magnetic resonance study showed that a peptide derived from the S4–S5 linker had no well‐ordered structure in aqueous solution and adopted a 310‐helix (E544‐Y545‐G546) structure in detergent micelles. The existence of an amphipathic helix was confirmed, which may be important for interaction with cell membrane. Close contact between side chains of residues R541 and E544 was observed, which may be important for its regulation of channel gating. Copyright © 2011 European Peptide ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5374713 Thu, 03 Nov 2011 04:00:00 +0100 5374713 http://www.medworm.com/index.php?rid=5374718&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1413 A set of analogues of the 14‐residue peptaibol tylopeptin B, containing the stable free‐radical 4‐amino‐1‐oxyl‐2,2,6,6,‐tetramethylpiperidine‐4‐carboxylic acid (TOAC) at one or two selected positions, was synthesized by the solid‐phase methodology. A solution conformational analysis performed by FTIR absorption and CD suggests that, in membrane‐mimicking solvents, the labeled tylopeptin B analogues preserve the helical propensity of the parent peptide, with a preference for the α‐helix or the 310‐helix type depending upon the nature of the solvent. In aqueous environment, the spin‐labeled analogues present a higher content of helical conformation as a consequence of the strong helix promoter effect of the conformationally constrained TOAC residue. We observed a... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5374718 Wed, 02 Nov 2011 04:00:00 +0100 5374718 http://www.medworm.com/index.php?rid=5374717&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1424 Fibril formation is the hallmark of pathogenesis in Alzheimer's disease and other amyloid disorders caused by conformational alterations leading to the aggregation of soluble monomers. Aβ40 self‐associates to form amyloid fibrils. Its central seven‐residue segment KLVFFAE (Aβ16–22), which is thought to be crucial for fibril formation of the full‐length peptide, forms fibrils even in isolation. Context‐dependent induction of amyloid formation by such sequences in peptides, which otherwise do not have that propensity, is of considerable interest. We have examined the effect of introducing the Aβ16–22 sequence at the N‐terminus of two amphipathic helical 18‐residue peptides Ac‐WYSEMKRNVQRLERAIEE‐am and Ac‐KQLIRFLKRLDRNLWGLA‐am, which have high average hydrophobic mo... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5374717 Wed, 02 Nov 2011 04:00:00 +0100 5374717 http://www.medworm.com/index.php?rid=5374716&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1411 IL‐15 is a proinflammatory cytokine that acts early in the inflammatory response and has been associated with several autoimmune diseases including rheumatoid arthritis, where it had been proposed as a therapeutic target. We recently reported an IL‐15 antagonist peptide corresponding to sequence 36–45 of IL‐15 (KVTAMKCFLL) named P8, which specifically binds to IL‐15Rα and inhibits IL‐15 biological activity with a half maximal inhibitory concentration (IC50) of 130 µm in CTLL‐2 proliferation assay. In order to improve binding of peptide P8 to the receptor IL‐15Rα, we used an Ala scan strategy to study contribution of each individual amino acid to the peptide's antagonist effect. Here, we found that Phe and Cys are important for peptide binding to IL‐15Rα. We also inv... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5374716 Wed, 02 Nov 2011 04:00:00 +0100 5374716 http://www.medworm.com/index.php?rid=5374715&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1415 We report that SOC4‐glyco‐conjugate bearing two copies of the α2,6‐sialyllactose is specifically recognized by the biotinylated Sambucus nigra (elderberry) bark lectin, which binds preferentially to sialic acid in an α2,6‐linkage. SOC4‐glyco‐conjugate bearing two copies of the α2,3‐sialyllactose was not recognized by the biotinylated Maackia amurensis lectin, despite its well‐known α2,3‐sialyl bond specificity. However, preliminary immune blot assays showed that H1N1 virus binds to both the SOC4‐glyco‐conjugates immobilized onto nitrocellulose membrane. It is concluded that Ac‐SOC4[(Ac)2,(3′SL‐Aoa)2]‐NH2 5 and Ac‐SOC4[(Ac)2,(6′SL‐Aoa)2]‐NH2 6 mimic the HA receptors. These findings could be useful for easy screening of binding and inhibition assays ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5374715 Wed, 02 Nov 2011 04:00:00 +0100 5374715 http://www.medworm.com/index.php?rid=5374712&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1417 Two selective agonists of nonopioid β‐endorphin receptor, synthetic peptides TPLVTLFK (octarphin) and SLTCLVKGFY (immunorphin), were labeled with tritium to specific activity of 29 and 25 Ci/mmol, respectively. Both labeled peptides were found to bind to high‐affinity naloxone‐insensitive binding sites on the membranes isolated from the rat myocardium (Kd = 2.0 ± 0.2 and 2.5 ± 0.3 nM, respectively). The [3H]octarphin specific binding to the myocardial membranes was inhibited by unlabeled β‐endorphin (Ki = 1.9 ± 0.2 nM) and immunorphin (Ki = 2.2 ± 0.3 nM). The [3H]immunorphin specific binding with the membranes was inhibited by unlabeled β‐endorphin (Ki = 2.3 ± 0.3 nM) and octarphin (Ki = 2.4 ± 0.3 nM). The binding s... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5374712 Tue, 01 Nov 2011 04:00:00 +0100 5374712 http://www.medworm.com/index.php?rid=5355056&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1412 A methodology is presented for the facile synthesis of Arg‐containing peptides modified at the guanidine headgroup as substituted amidine cores. This process allows for the iterative construction of these Arg isosteres while the peptide is being built out on the solid support, providing a high potential for diversity in substitution pattern in the resulting peptide. A series of N‐Pmc‐substituted thioamides were condensed with deprotected δ‐N Orn‐bearing peptides while attached to the solid support using Mukaiyama's reagent as coupling reagent, yielding isosteric Arg‐containing analogs. Peptides were cleaved using trimethylsilyl trifluoromethanesulfonate/TFA and analyzed in their crude form in order to illustrate the amenability of this process toward production of peptide isol... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5355056 Thu, 27 Oct 2011 23:26:54 +0100 5355056 http://www.medworm.com/index.php?rid=5355058&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1401 Purification of pluripotent stem cell (PSC)‐derived cardiomyocytes is critical for the application of cardiomyocytes both in clinical and basic research. Finding a specific cell marker is a promising method for purifying induced cells. The present study employed phage display technology to search for particular cell markers that could bind specifically to PSC‐derived cardiomyocytes. After three rounds of biopanning, several peptides were obtained. The ELISA results show the no. 3 sequence peptide (QPFTTSLTPPAR), and other four sequences having a consensus motif [SS(Q)PPQ(S)], no. 9, 11, 14, and 10, have relatively high affinity and specificity to cardiomyocytes. Immunofluorescence confirmed that the selected peptides could bind specifically to the PSC‐derived cardiomyocytes. Competit... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5355058 Thu, 27 Oct 2011 04:00:00 +0100 5355058 http://www.medworm.com/index.php?rid=5355057&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1410 We extended the use of Peplook, an in silico procedure for the prediction of three‐dimensional (3D) models of linear peptides to the prediction of 3D models of cyclic peptides and thanks to the ab initio calculation procedure, to the calculation of peptides with non‐proteinogenic amino acids. Indeed, such peptides cannot be predicted by homology or threading. We compare the calculated models with NMR and X‐ray models and for the cyclic peptides, with models predicted by other in silico procedures (Pep‐Fold and I‐Tasser). For cyclic peptides, on a set of 38 peptides, average root mean square deviation of backbone atoms (BB‐RMSD) was 3.8 and 4.1 Å for Peplook and Pep‐Fold, respectively. The best results are obtained with I‐Tasser (2.5 Å) although evaluations were biased... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5355057 Thu, 27 Oct 2011 04:00:00 +0100 5355057 http://www.medworm.com/index.php?rid=5292611&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1399 Chlamydia trachomatis ribonucleotide reductase (RNR) is a class Ic RNR. It has two homodimeric subunits: proteins R1 and R2. Class Ic protein R2 in its most active form has a manganese–iron metal cofactor, which functions in catalysis like the tyrosyl radical in classical class Ia and Ib RNRs. Oligopeptides with the same sequence as the C‐terminus of C. trachomatis protein R2 inhibit the catalytic activity of C. trachomatis RNR, showing that the class Ic enzyme shares a similar highly specific inhibition mechanism with the previously studied radical‐containing class Ia and Ib RNRs. The results indicate that the catalytic mechanism of this class of RNRs with a manganese–iron cofactor is similar to that of the tyrosyl‐radical‐containing RNRs, involving reversible long‐range... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5292611 Tue, 04 Oct 2011 04:00:00 +0100 5292611 http://www.medworm.com/index.php?rid=5292610&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1400 Hepatocellular carcinoma is a common malignancy. The carcinoma cells express glypican‐3 (GPC‐3) on the cell membrane. GPC‐3 is also expressed in melanoma cells. Therefore, GPC‐3 might be a potential target for tumor imaging or therapy. Here, proteomic mass spectrometry was used to identify peptides that target GPC‐3‐expressing tumors. A mammalian expression vector expressing a FLAG‐GPC‐3 fusion protein was cloned for immunoprecipitation. With the use of liposomes, the vector was transfected into HepG2 (HepG2/FLAG‐GPC‐3) and HEK 293 cells, and the transfected cell lines were selected with geneticin. HepG2/FLAG‐GPC‐3 cells were used for immunoprecipitation of FLAG‐GPC‐3 fusion protein. Seven peptide candidates (L1–L7) were selected for GPC‐3‐targeting ligand... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5292610 Tue, 04 Oct 2011 04:00:00 +0100 5292610 http://www.medworm.com/index.php?rid=5321229&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1402 De novo design of peptides and proteins has recently surfaced as an approach for investigating protein structure and function. This approach vitally tests our knowledge of protein folding and function, while also laying the groundwork for the fabrication of proteins with properties not precedented in nature. The success relies heavily on the ability to design relatively short peptides that can espouse stable secondary structures. To this end, substitution with α,β‐didehydroamino acids, especially α,β‐didehydrophenylalanine (ΔzPhe), comes in use for spawning well‐defined structural motifs. Introduction of ΔPhe induces β‐bends in small and 310‐helices in longer peptide sequences. The present work aims to investigate the effect of nature and the number of amino acids interspe... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5321229 Sat, 01 Oct 2011 04:00:00 +0100 5321229 http://www.medworm.com/index.php?rid=5292609&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1407 Pemetrexed (Pem) is a novel antimetabolite type of anticancer drug that demonstrated promising clinical activity in a wide variety of solid tumors, including non‐small cell lung carcinoma and malignant pleural mesothelioma. It inhibits enzymes involved in the folate pathway, for which the presence of its free carboxylic groups is necessary. The heteroaromatic ring system of Pem has a modifiable amino group, which opens a possibility to apply a new strategy to conjugate Pem to carrier molecules. Considering this as well as the necessity of untouched carboxylic groups of Pem in the new conjugates, we developed a new synthesis strategy. Here, we describe the synthesis and the characterization of new Pem‐peptide conjugates in which cell‐penetrating octaarginine or/and lung‐targeting H�... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5292609 Sat, 01 Oct 2011 04:00:00 +0100 5292609 http://www.medworm.com/index.php?rid=5268337&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1406 In this study, we synthesized sublancin by Fmoc‐based solid‐phase peptide synthesis and chemoselective disulfide formation reactions. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.Sublancin is an S‐linked glycopeptide produced by Bacillus subtilis 168 and consists of 37 amino acid residues with two disulfide bonds. In this study, we synthesized sublancin by Fmoc‐based solid‐phase peptide synthesis and chemoselective disulfide formation reactions. (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5268337 Fri, 30 Sep 2011 08:43:37 +0100 5268337 http://www.medworm.com/index.php?rid=5268341&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1405 Thermal stability of the α‐helix conformation of melittin in pure ethanol and ethanol–water mixture solvents has been investigated by using NMR spectroscopy. With increase in water concentration of the mixture solvents (from 0 wt% to ~71.5 wt%) as well as temperature (from room temperature to 60 °C), the intramolecular hydrogen bonds formed in melittin are destabilized and the α‐helix is partially uncoiled. Further, the hydrogen bonds are found to be more thermally stable in pure ethanol than in pure methanol, suggesting that their stability is enhanced with increase in the size of the alkyl groups of alcohol molecules. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.Melittin maintains a full α‐helix up to 60 °C at least in pure ethanol. With ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5268341 Thu, 29 Sep 2011 04:00:00 +0100 5268341 http://www.medworm.com/index.php?rid=5268340&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1408 pVEC is a cell‐penetrating peptide derived from the murine vascular endothelial‐cadherin protein. To evaluate the potential of pVEC as antimicrobial peptide (AMP), we synthesized pVEC and its analogs with Trp and Arg/Lys substitution, and their antimicrobial and lipopolysaccharide (LPS)‐neutralizing activities were investigated. pVEC and its analogs displayed a potent antimicrobial activity (minimal inhibitory concentration: 4–16 μM) against Gram‐positive and Gram‐negative bacteria but no or less hemolytic activity (less than 10% hemolysis) even at a concentration of 200 μM. These peptides induced a near‐complete membrane depolarization (more than 80%) at 4 μM against Staphylococcus aureus and a significant dye leakage (35–70%) from bacterial membrane‐mimicking l... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5268340 Thu, 29 Sep 2011 04:00:00 +0100 5268340 http://www.medworm.com/index.php?rid=5268339&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1404 Tyrosinase plays a critical role in the early stages of the melanin synthetic pathway by catalyzing the oxidation of the substrate. Therefore, tyrosinase inhibitors have been intensively studied in both cosmetic and food industries to develop hypopigmentary agents and prevent enzymatic browning in food. Previously, we reported that kojic acid–amino acid amide (KA‐AA‐NH2) showed enhanced tyrosinase inhibitory activity compared with kojic acid alone, but this was not observed in a cell test because of poor cell permeability. To enhance cell permeability, we prepared copper and zinc complexes of KA‐AA‐NH2 and characterized them using FT‐IR spectroscopy, ESI‐MS spectrometry, and inductively coupled plasma analysis. We then showed that KA‐AA‐NH2 copper complexes exhibited mela... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5268339 Thu, 29 Sep 2011 04:00:00 +0100 5268339 http://www.medworm.com/index.php?rid=5268338&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1409 In this study, two novel antimicrobial peptides from the skin secretions of the marsh frog, Rana ridibunda, named temporin‐Ra and temporin‐Rb, were identified and purified using RP‐HPLC. Temporin‐Ra and temporin‐Rb are composed of 14 and 12 amino acids, respectively. Our results show that these peptides have inhibitory effects on both gram‐negative and gram‐positive bacteria, especially antibiotic resistant strains prevalent in hospitals, such as Staphylococcus aureus and Streptococcus agalactiae. The sequences and molecular weights of these peptides were determined using tandem MS. The molecular masses were found to be 1242.5 Da for temporin‐Rb and 1585.1 Da for temporin‐Ra. Human red blood cells tolerated well exposure to temporin‐Ra and temporin‐Rb, which, at a... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5268338 Thu, 29 Sep 2011 04:00:00 +0100 5268338 http://www.medworm.com/index.php?rid=5233053&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1397 This study is focused in the presence of phospholipid‐peptide complexes in wheat sprouts extract. For example, a peptide molecular model was obtained from the MS/MS spectrum of the ion with m/z 905.5 (Figure 7); the series of ions at m/z 906.6 (molecular ion MH+), 311.3, 414.5, 511.3, 568.1, 625.3 (N‐terminal fragments) and 596.1, (C‐terminal fragment) is compatible with the sequence pyroGlu‐Ala‐Gln (orGln‐Ala)‐Cys‐Pro‐Gly‐Gly‐Phe‐AsnOH. Potential complexes of this peptide with lysophospatidylcholine (LPC) or phosphatidylcholine (PC) were recognized in the RP HPLC fractions of wheat sprouts extract as monocharged ion m/z 1428.93 and bicharged ion m/z 833.22 ( Table 1) : m/z 1428.93: [ion 905.55 + LPC(C18:0) + H]+m/z 833.22 : [ion 905.55 + PC(C16:0/C18:2) + 2H]2+ (So... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5233053 Wed, 14 Sep 2011 04:00:00 +0100 5233053 http://www.medworm.com/index.php?rid=5246001&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1391 AbstractApolipoprotein A‐I (apoA‐I), which constitutes the principal protein component of high‐density lipoprotein, is responsible for its major antiatherogenic functions. Aiming at contributing to the development of potent inhibitors of low‐density lipoprotein (LDL) peptide models of helices 4,6 and 9,10 of apoA‐I were designed and synthesized. Specific amino acid substitutions, resulting in transformation of the original helix class A and Y to G according to the Schiffer and Edmundson helical wheel representation, were introduced in order to validate the contribution of these modifications in the inhibitory activity of the synthesized peptide models against the LDL oxidation. The role of Met at positions 112 (helix 4) and 148 (helix 6) as oxidant scavenger was also investigated... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5246001 Thu, 01 Sep 2011 04:00:00 +0100 5246001 http://www.medworm.com/index.php?rid=5233052&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1394 AbstractThe elastin precursor tropoelastin possesses a number of polymeric peptides with repeating 3–9 mer sequences. One of these is the pentapeptide Val‐Pro‐Gly‐Val‐Gly (VPGVG) present in almost all animal species, and its polymer (VPGVG)n coacervates just as does tropoelastin. In the present study, in order to explore the structural requirements essential for coacervation, (VPGVG)n and its shortened repeat analogs (VPGV)n, (VPG)n, and (PGVG)n were synthesized and their structural properties were investigated. In our turbidity measurements, (VPGVG)n demonstrated complete reversible coacervation in agreement with previous findings. The Gly5‐deleted polymer (VPGV)n also achieved self‐association, though the onset of self‐association occurred at a lower temperature. However,... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5233052 Thu, 01 Sep 2011 04:00:00 +0100 5233052 http://www.medworm.com/index.php?rid=5085114&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1386 AbstractId1 proteins, inhibitors of differentiation or DNA binding, act as dominant negative antagonists of the bHLH family of transcription factors, which play an important role in cellular development, proliferation, and differentiation. The mechanism of Id proteins is to antagonize bHLH proteins by forming high‐affinity heterodimers with other bHLH proteins, thereby preventing them from binding to DNA and inhibiting transcription of differentiation‐associated genes. Our goal is to study the SARs of a peptidic antagonist of Id1, peptide 3C, which exhibits high affinity for Id1 and inhibitory effect on the proliferation of cancer cells. A series of N‐terminal‐ and C‐terminal‐deleted analogs of peptide 3C were designed, synthesized, and characterized. Affinity of each peptide f... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5085114 Sun, 31 Jul 2011 23:00:00 +0100 5085114 http://www.medworm.com/index.php?rid=5085113&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1395 AbstractAttracted by the possibility to optimize time and yield of the synthesis of difficult peptide sequences by MW irradiation, we compared Fmoc/tBu MW‐assisted SPPS of 1–34 N‐terminal fragment of parathyroid hormone‐related peptide (PTHrP) with its conventional SPPS carried out at RT. MWs were applied in both coupling and deprotection steps of SPPS protocol. During the stepwise elongation of the resin‐bound peptide, monitoring was conducted by performing MW‐assisted mini‐cleavages and analyzing them by UPLC‐ESI‐MS. Identification of some deletion sequences was helpful to recognize critical couplings and as such helped to guide the introduction of MW irradiations to these stages. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.In this paper, w... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5085113 Sun, 31 Jul 2011 23:00:00 +0100 5085113 http://www.medworm.com/index.php?rid=5085112&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1392 This article addresses the interactions of the synthetic antimicrobial peptide dermaseptin 01 (GLWSTIKQKGKEAAIAAA‐ KAAGQAALGAL‐NH2, DS 01) with phospholipid (PL) monolayers comprising (i) a lipid‐rich extract of Leishmania amazonensis (LRE‐La), (ii) zwitterionic PL (dipalmitoylphosphatidylcholine, DPPC), and (iii) negatively charged PL (dipalmitoylphosphatidylglycerol, DPPG). The degree of interaction of DS 01 with the different biomembrane models was quantified from equilibrium and dynamic liquid‐air interface parameters. At low peptide concentrations, interactions between DS 01 and zwitterionic PL, as well as with the LRE‐La monolayers were very weak, whereas with negatively charged PLs the interactions were stronger. For peptide concentrations above 1 µg/ml, a considerable ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5085112 Sun, 31 Jul 2011 23:00:00 +0100 5085112 http://www.medworm.com/index.php?rid=5085111&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1390 Abstractα,β‐Dehydroamino acid esters occur in nature. To investigate their conformational properties, a systematic theoretical analysis was performed on the model molecules Ac‐ΔXaa‐OMe [ΔXaa = ΔAla, (E)‐ΔAbu, (Z)‐ΔAbu, ΔVal] at the B3LYP/6‐311+ + G(d,p) level in the gas phase as well as in chloroform and water solutions with the self‐consistent reaction field‐polarisable continuum model method. The Fourier transform IR spectra in CCl4 and CHCl3 have been analysed as well as the analogous solid state conformations drawn from The Cambridge Structural Database. The ΔAla residue has a considerable tendency to adopt planar conformations C5 (ϕ, ψ ≈ − 180°, 180°) and β2 (ϕ, ψ ≈ − 180°, 0°), regardless of the environment. The ΔVal residue prefers the conf... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5085111 Sun, 31 Jul 2011 23:00:00 +0100 5085111 http://www.medworm.com/index.php?rid=5085110&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1396 AbstractC‐2 dimethylated/unmethylated thiazolidine‐4‐carboxylic acid and C‐2 dimethylated oxazolidine‐4‐carboxylic acid were introduced into the insect kinin core pentapeptide in place of Pro3, yielding three new analogues. NMR analysis revealed that the peptide bond of Phe2‐pseudoproline (ΨPro)3 is practically 100% in cis conformation in the case of dimethylated pseudoproline‐containing analogues, about 50% cis for the thiazolidine‐4‐carboxylic acid analogue and about 33% cis for the parent Pro3 peptide. The diuretic activities are consistent with the population of cis conformation of the Phe2‐ΨPro3/Pro3 peptide bonds, and the results confirm a cis Phe‐Pro bond as bioactive conformation. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.Th... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5085110 Sun, 31 Jul 2011 23:00:00 +0100 5085110 http://www.medworm.com/index.php?rid=5085109&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1398 AbstractGiven the paucity and toxicity of available drugs for leishmaniasis, coupled with the advent of drug resistance, the discovery of new therapies for this neglected tropical disease is recognised as being of the utmost urgency. As such antimicrobial peptides (AMPs) have been proposed as promising compounds against the causative Leishmania species, insect vector‐borne protozoan parasites. Here the AMP temporins A, B and 1Sa have been synthesised and screened for activity against Leishmania mexicana insect stage promastigotes and mammalian stage amastigotes, a significant cause of human cutaneous disease. In contrast to previous studies with other species the activity of these AMPs against L. mexicana amastigotes was low. This suggests that amastigotes from different Leishmania speci... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5085109 Sun, 31 Jul 2011 23:00:00 +0100 5085109 http://www.medworm.com/index.php?rid=5048030&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1389 AbstractDepsidomycin is a cyclic heptadepsi‐peptide isolated from the cultured broth of Streptomyces lavendofoliae MI951‐62F2. It exhibits significant antimicrobial and immunosuppressive activity. The total synthesis of a depsidomycin analogue in which 1,2‐piperazine‐3‐carboxylic acid was substituted with proline is described. After several trials using different strategies, the desired depsidomycin analogue was obtained via stepwise synthesis starting by the amino acid ‘head’ and macrolactonization under Yamaguchi conditions. The cyclic depsipeptide was evaluated to have an minimum inhibitory concentration (MIC) of 4 µg/ml against H37RV and 16 µg/ml against MDR clinical strains of MTB (MDR‐MTB), while the linear precursor 8 also had MICs of 4 and 16 µg/ml for the suscep... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5048030 Thu, 21 Jul 2011 23:11:35 +0100 5048030 http://www.medworm.com/index.php?rid=5048033&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1387 In this study, we investigated the anti‐inflammatory activities of 9Pbw2, 9Pbw3, and 9Pbw4 by quantitation of NO production in LPS‐stimulated RAW264.7 cells. The results showed that only 9Pbw3 has strong inhibition of NO production, implying that Trp7 as well as optimum level of hydrophobicity may play key roles in the anti‐inflammatory activity of 9Pbw3. In order to design potent anti‐inflammatory peptide with lower cytotoxicity as well as high stability from cleavage by protease compared to 9Pbw3, we synthesized 9Pbw3‐D, the all‐D‐amino acid analog of 9Pbw3. 9Pbw3‐D showed less cytotoxicity against RAW264.7 cells as well as considerably stronger inhibition of NO production and inflammation‐induced cytokine production in LPS‐stimulated RAW264.7 cells than 9Pbw3. 9Pbw3�... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5048033 Sat, 16 Jul 2011 23:00:00 +0100 5048033 http://www.medworm.com/index.php?rid=5048032&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1388 This article describes the role of the His residue at position 1 of the alloferon peptide chain and new antiviral properties of alloferon and its analogues. Biological effect of these peptides was evaluated in vitro by the antiviral test against DNA and RNA viruses using cell lines. It was found that most of the evaluated peptides inhibit the replication of DNA‐ and RNA viruses in vitro and the most active compound was [Lys1]‐alloferon. (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5048032 Sat, 16 Jul 2011 23:00:00 +0100 5048032 http://www.medworm.com/index.php?rid=5048031&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1393 AbstractNanopore analysis is an emerging technique of structural biology which employs nanopores, such as the α‐hemolysin pore, as a biosensor. A voltage applied across a membrane containing a nanopore generates a current, which is partially blocked when a molecule interacts with the pore. The magnitude (I) and the duration (T) of the current blockade provide an event signature for that molecule. Two peptides, CY12(+)T1 and CY12(−)T1 with net charges + 2 and − 2, respectively, were analysed using different applied voltages and all four possible orientations of the electrodes and pore. The four orientations were vestibule downstream (VD), vestibule upstream (VU), stem downstream (SD) and stem upstream (SU) where vestibule and stem refer to the side of the pore on which the peptide wa... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=5048031 Sat, 16 Jul 2011 23:00:00 +0100 5048031 http://www.medworm.com/index.php?rid=4919879&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1383 We describe here the chemical synthesis of such a 53 residue long TCERG1 WW‐3 domain sequence that exhibits the typical WW domain fold, and could be useful for discovering cellular targets. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.Folding of the TCERG1 WW‐3 domain depends strongly on the sequence borderlines used for synthesis. A C‐terminally sequence elongation including an α‐helical structure is crucial for proper folding. We describe here the chemical synthesis of a new 53 residue long TCERG1 WW‐3 domain sequence that exhibits the typical WW domain fold, and could be useful for discovering cellular targets. (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4919879 Thu, 09 Jun 2011 23:00:00 +0100 4919879 http://www.medworm.com/index.php?rid=4919878&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1384 AbstractTo clarify the higher eukaryotic initiation factor 4E (eIF4E) binding selectivity of 4E‐binding protein 2 (4E‐BP2) than of 4E‐BP1, as determined by Trp fluorescence analysis, the crystal structure of the eIF4E binding region of 4E‐BP2 in complex with m7GTP‐bound human eIF4E has been determined by X‐ray diffraction analysis and compared with that of 4E‐BP1. The crystal structure revealed that the Pro47‐Ser65 moiety of 4E‐BP2 adopts a L‐shaped conformation involving extended and α‐helical structures and extends over the N‐terminal loop and two different helix regions of eIF4E through hydrogen bonds, and electrostatic and hydrophobic interactions; these features were similarly observed for 4E‐BP1. Although the pattern of the overall interaction of 4E‐BP2 w... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4919878 Thu, 09 Jun 2011 23:00:00 +0100 4919878 http://www.medworm.com/index.php?rid=4910200&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1378 In this report we describe the synthesis of an orthogonally protected α,α‐disubstituted amino acid building block serving as labionin precursor for the future assembly of labyrinthopeptin A2 and of other labyrinthopeptin derivatives. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.The labyrinthopeptins are a new class of lantibiotics containing two identical quaternary α,α‐disubstituted amino acids, named labionin (Lab). The synthetic formation of this unique structural feature represents the key step in the total synthesis of these polycyclic peptides. In this report we describe the synthesis of an orthogonally protected α,α‐disubstituted amino acid building block serving as labionin precursor for the future assembly of labyrinthopeptin A2 and of othe... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4910200 Sun, 05 Jun 2011 23:00:00 +0100 4910200 http://www.medworm.com/index.php?rid=4910199&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1376 AbstractAn improved synthesis of (2S, 4S)‐ and (2S, 4R)‐2‐amino‐4‐methyldecanoic acids was accomplished using a glutamate derivative as starting material and Evans' asymmetric alkylation as the decisive step. The NMR data of the two diastereomers were measured and compared with those of the natural product. As a result, the stereochemistry of this novel amino acid unit in culicinins was assigned as (2S, 4R). Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.An improved synthesis of (2S, 4S)‐ and (2S, 4R)‐2‐amino‐4‐methyldecanoic acids was accomplished using a glutamate derivative as starting material and Evans' asymmetric alkylation as the decisive step. The NMR data of the two diastereomers were measured and compared with those of the natural pr... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4910199 Sun, 05 Jun 2011 23:00:00 +0100 4910199 http://www.medworm.com/index.php?rid=4910198&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1381 AbstractP14C/N39C is the disulfide variant of the ovomucoid third domain from silver pheasant (OMSVP3) introducing an engineered Cys14Cys39 bond near the reactive site on the basis of the sequence homology between OMSVP3 and ascidian trypsin inhibitor. This variant exhibits a narrower inhibitory specificity. We have examined the effects of introducing a Cys14Cys39 bond into the flexible N‐terminal loop of OMSVP3 on the thermodynamics of the reactive site peptide bond hydrolysis, as well as the thermal stability of reactive site intact inhibitors. P14C/N39C can be selectively cleaved by Streptomyces griseus protease B at the reactive site of OMSVP3 to form a reactive site modified inhibitor. The conversion rate of intact to modified P14C/N39C is much faster than that for wild type u... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4910198 Sun, 05 Jun 2011 23:00:00 +0100 4910198 http://www.medworm.com/index.php?rid=4910197&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1379 AbstractProlonged oral creatine administration resulted in remarkable neuroprotection in experimental models of brain stroke. However, because of its polar nature creatine has poor ability to penetrate the blood–brain barrier (BBB) without specific creatine transporter (CRT). Thus, synthesis of hydrophobic derivatives capable of crossing the BBB by alternative pathway is of great importance for the treatment of acute and chronic neurological diseases including stroke, traumatic brain injury and hereditary CRT deficiency. Here we describe synthesis of new hybrid compounds—creatinyl amino acids, their neuroprotective activity in vivo and stability to degradation in different media. The title compounds were synthesized by guanidinylation of corresponding sarcosyl peptides or direct creati... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4910197 Sun, 05 Jun 2011 23:00:00 +0100 4910197 http://www.medworm.com/index.php?rid=4910196&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1382 AbstractThe increasing interest in click chemistry and its use to stabilize turn structures led us to compare the propensity for β‐turn stabilization of different analogs designed as mimics of the β‐turn structure found in tendamistat. The β‐turn conformation of linear β‐amino acid‐containing peptides and triazole‐cyclized analogs were compared to ‘conventional’ lactam‐ and disulfide‐bridged hexapeptide analogs. Their 3D structures and their propensity to fold in β‐turns in solution, and for those not structured in solution in the presence of α‐amylase, were analyzed by NMR spectroscopy and by restrained molecular dynamics with energy minimization. The linear tetrapeptide Ac‐Ser‐Trp‐Arg‐Tyr‐NH2 and both the amide bond‐cyclized, c[Pro‐Ser‐Trp‐... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4910196 Sun, 05 Jun 2011 23:00:00 +0100 4910196 http://www.medworm.com/index.php?rid=4910195&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1377 In conclusion, the XxxYyy16 salt‐bridge is not an isolated entity of this fold; rather it is an integrated part of a complex interaction network. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.Network anchoring: Designed Trp‐cage miniproteins bearing different amino acids at positions 9 and 16 were used to test the stabilization power of a salt‐ bridge in a context dependent manner. An H‐bonding network has been scru‐ tinized. Cooperativity network of Trp‐ cage miniproteins probing salt‐bridges. (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4910195 Sun, 05 Jun 2011 23:00:00 +0100 4910195 http://www.medworm.com/index.php?rid=4919877&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1385 We report that substitution of Ex‐4 amino acids Glu16, Leu21, and Glu24 to the GLP‐1 sequence enabled Gly2 tolerance. The coordination of the N‐terminus with these central residues shows an interaction of substantial importance not only to DPP‐IV stability but also to receptor activation. Extension of this observation to glucagon‐based co‐agonist peptides showed different structural requirements for effective communication between the N‐terminus and the mid‐section of these peptides in achieving high potency agonism at the GLP‐1 and GCGRs. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.Biochemical signaling at glucagon‐related peptide receptors is highly dependent on proper orientation of the peptide's N‐terminal histidine within the recepto... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4919877 Tue, 31 May 2011 23:00:00 +0100 4919877 http://www.medworm.com/index.php?rid=4910194&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1380 AbstractTwo antimicrobial peptides (piceain 1 and 2) derived from sequences encoded Picea sitchensis are identified. Their amino acid sequences are KSLRPRCWIKIKFRCKSLKF and RPRCWIKIKFRCKSLKF, respectively. One intra‐molecular disulfide bridge is formed by these two half‐cysteines in both piceain 1 and 2. Antimicrobial activities of synthesized piceains against several kinds of microorganisms were tested. They showed antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and fungus Candida albicans but little antimicrobial activity against Bacillus subtilis. The results of nematicidal test showed they exerted strong nematicidal activities against Caenorhabditis elegans, following exposure for 5 h at concentrations as low as 10 µg/ml. They had ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4910194 Tue, 31 May 2011 23:00:00 +0100 4910194 http://www.medworm.com/index.php?rid=4819448&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1375 AbstractHTLV‐I is a debilitating and/or lethal retrovirus that causes HTLV‐I‐associated myelopathy/tropical spastic paraparesis, adult T‐cell leukemia and several inflammatory diseases. HTLV‐I protease is an aspartic retropepsin involved in HTLV‐I replication and its inhibition could treatHTLV‐I infection. A recombinant L40I mutant HTLV‐I protease was designed and obtained from Escherichia coli, self‐processingand purification by ion‐exchange chromatography. The protease was refolded by a one‐step dialysis and recovered activity. The cleavage efficiency of the [Ile40]HTLV‐I protease was at least 300 times higher for a fluorescent substratethan that of our previously reported recombinant His‐tagged non‐mutated HTLV‐I protease. In addition, we designed and synth... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4819448 Fri, 13 May 2011 20:37:30 +0100 4819448 http://www.medworm.com/index.php?rid=4819449&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1374 AbstractA 7‐mer peptide (S‐T‐L‐P‐L‐P‐P) that bound to various divalent cations was selected from a phage display peptide library. Isothermal calorimetric analysis revealed that the peptide bound to Pb2+, Cd2+, Hg2+, and Cu2+. Through the use of CD studies, no secondary structural changes were observed for the peptide upon binding to divalent cations. Ala scanning mutant peptides bound to Hg2+ with a reduced affinity. However, no single substitution was shown to affect the overall affinity. We suggest that Pro residues chelate divalent cations, while the structure formed by the peptide is also important for the binding process. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.A 7‐mer peptide (S‐T‐L‐P‐L‐P‐P) was selected for binding to div... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4819449 Thu, 12 May 2011 23:00:00 +0100 4819449 http://www.medworm.com/index.php?rid=4762141&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1370 AbstractThe defensin‐like antimicrobial peptides have been characterized from various other arthropods including insects, scorpions, and ticks. But no natural spider defensin‐like antimicrobial peptides have ever been isolated from spiders, except couple of cDNA and DNA sequences of five spider species revealed by previous genomic study. In this work, a defensin‐like antimicrobial peptide named Oh‐defensin was purified and characterized from the venoms of the spider, Ornithoctonus hainana. Oh‐defensin is composed of 52 amino acid (aa) residues including six Cys residues that possibly form three disulfide bridges. Its aa sequence is MLCKLSMFGAVLGV PACAIDCLPMGKTGGSCEGGVCGCRKLTFKILWDKKFG. By BLAST search, Oh‐defensin showed significant sequence similarity to other arthropod antimi... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4762141 Thu, 28 Apr 2011 23:18:45 +0100 4762141 http://www.medworm.com/index.php?rid=4762145&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1359 AbstractThe role of silver ions in various pathologies, as well as their effect on peptide conformation and properties are less understood. Consequently, we synthesized several peptides with various residues in their sequence to investigate silver‐induced conformational changes at various pH values by Circular Dichroism spectroscopy. Uniquely, the glycine‐based, histidine‐containing peptide showed a severe change from a random coil and β‐turn conformation to large α‐helices during silver binding. When comparing the effect of silver ions on the conformation of bradykinin a similar tendency was found. Besides, silver ions reduced the amyloid‐β peptide tendency to aggregation. Our results suggest a specific and protective role for silver ions in brain pathologies, which is rela... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4762145 Wed, 27 Apr 2011 23:00:00 +0100 4762145 http://www.medworm.com/index.php?rid=4762144&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1365 AbstractThe aromatic amino acids Tyr and Phe in angiotensin IV (Ang IV) were conformationally constrained by the use of β‐Me substituted analogs, or cyclic constrained analogs. None of these modifications was allowed for Tyr1, while only e‐β‐MePhe6 substitution resulted in an AngIV analog with high IRAP potency and selectivity versus AP‐N or the AT1 receptor. This indicates an important role of the orientation of the Phe6 for inducing selectivity. Pro5 replacement with 2‐aminocyclopentanecarboxylic acid maintained IRAP potency and abolished AT1 affinity. These results confirm the importance of conformational constrained amino acids to generate selectivity in bioactive peptides. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.To develop selective Ang IV... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4762144 Wed, 27 Apr 2011 23:00:00 +0100 4762144 http://www.medworm.com/index.php?rid=4762143&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1371 In this study, ten tetra‐ and heptapeptide analogues of deltorphin containing the urea bridges between residues 2 and 4 have been docked into the δ‐ and µ‐opioid receptors to explain their different biological activities. The important factors explaining particular ligand activity such as free energy of binding, conformation of the ligand, its location inside the binding pocket as well as the number and strength of the receptor–ligand interactions have been discussed. Several different binding modes for investigated ligands have been proposed. It appears that the binding site is not identical even for very similar ligands. Results of this study help to explain the differences in biological activity of the deltorphin analogues, their interaction with the opioid receptors at the mo... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4762143 Wed, 27 Apr 2011 23:00:00 +0100 4762143 http://www.medworm.com/index.php?rid=4762142&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1368 AbstractWe have recently reported on a class of IgE‐binding peptides designed based on the crystallographic structure of the high affinity FcεRI. Peptides contain receptor key residues located within the two distinct binding sites for IgE and selectively bind IgE with an affinity ranging between 6 and 60 µM. We have here designed and characterized a new molecule containing the receptor loops C′–E and B–C and an optimized linker for joining them made of a Lys side chain and a β‐Ala. This new peptide shows an increased affinity (around 30 times) compared to the parent loop C′–E + B–C previously described, while retaining the same two‐site mechanism of binding and the same selectivity. It also blocks the binding of IgE to the cell‐anchored receptor and efficiently preve... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4762142 Wed, 27 Apr 2011 23:00:00 +0100 4762142 http://www.medworm.com/index.php?rid=4713792&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1352 In this study, we investigated the protective effect of recombinant human glucagon‐like peptide‐1 (rhGLP‐1) treatment on STZ‐induced diabetic mice. Mice were treated daily with rhGLP‐1 (24 nmol/kg body weight) starting before or after STZ injection (40 mg/kg body weight) to induce diabetes. Mice pretreated with rhGLP‐1 before but not after STZ showed significantly reduced blood glucose levels (P < 0.05), increased oral glucose tolerance (area under the curve, 1740 ± 71.18 vs 2416 ± 205.6, P < 0.05). Furthermore, the bioproduct of lipid peroxidation, MDA, was reduced and SOD and GSH‐PX activities were enhanced globally and in pancreas of mice that received rhGLP‐1 pretreatment before STZ, when comparing with STZ‐treated mice. Finally, STZ‐induced pancreatic islet... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4713792 Fri, 15 Apr 2011 06:00:20 +0100 4713792 http://www.medworm.com/index.php?rid=4713796&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1362 AbstractThe development of a multigram synthesis of the orthogonally protected amino acid‐derived Phaol [2‐{[(2S)‐2‐amino‐3‐phenylpropyl]amino}ethanol] is described. The goal of this work is to synthesize an orthogonally protected Phaol in a multigram scale up to 10 g (Cbz‐Phaol), so it can be used in solution‐based peptide synthesis of peptaibols. Two synthetic schemes were proposed and examined. Between the reduction‐coupling and the coupling‐reduction scheme, the latter gave the best results. A two‐step synthesis affords easily purifiable products. Several analogs were synthesized using this methodology. All the molecules were orthogonally protected, so that they can be used in peptide synthesis. Deprotection posed no problems. Copyright © 2011 European Peptide So... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4713796 Wed, 13 Apr 2011 23:00:00 +0100 4713796 http://www.medworm.com/index.php?rid=4713795&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1364 AbstractThe medium‐length peptaibiotics are characterized by a primary structure of 14–16 amino acid residues. Despite the interesting antibiotic and antifungal properties exhibited by these membrane‐active peptides, their exact mechanism of action is still unknown. Here, we present our results on heptaibin, a 14‐amino acid peptaibiotic found to exhibit antimicrobial activity against Staphylococcus aureus. We carried out the very challenging synthesis of heptaibin on solid phase and a detailed conformational analysis in solution. The peptaibiotic is folded in a mixed 310‐/α‐helix conformation which exhibits a remarkable amphiphilic character. We also find that it is highly stable toward degradation by proteolytic enzymes and nonhemolytic. Finally, fluorescence leakage experime... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4713795 Wed, 13 Apr 2011 23:00:00 +0100 4713795 http://www.medworm.com/index.php?rid=4713794&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1361 AbstractOn the basis of the total synthesis of obyanamide, 20 analogues of this marine cyclic depsipeptide have been synthesized by (i) preparation of the tripeptide fragments in the western hemisphere using Z/OtBu protocol; (ii) preparation of the dipeptide fragments in the eastern hemisphere using Boc/OMe protocol; and (iii) fragments coupling, removal of protecting groups (Boc and OtBu, in one pot), and macrocyclizaion in the last step. The cytotoxic test showed that three synthetic compounds exhibited moderate activities against HL‐60, KB, LOVO, and A549 cell lines. According to the results, the β‐amino acid residue was found to play a critical role in the biological activities. Additionally, the ester bond along with the Ala(Thz) moiety was also essential for biological activitie... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4713794 Wed, 13 Apr 2011 23:00:00 +0100 4713794 http://www.medworm.com/index.php?rid=4713793&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1367 AbstractRegulatory pressure has compelled the chemical manufacturing industry to reduce the use of organic solvents in synthetic chemistry, and there is currently a strong focus on replacing these solvents with water. Here, we describe an efficient in‐water solution‐phase peptide synthesis method using Boc‐amino acids. It is based on a coupling reaction utilizing suspended water‐dispersible nanoparticle reactants. Using this method, peptides were obtained in good yield and with high purity. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.Regulatory pressure has compelled the chemical manufacturing industry to reduce the use of organic solvents in synthetic chemistry, and there is currently a strong focus on replacing these solvents with water. Here, we des... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4713793 Wed, 13 Apr 2011 23:00:00 +0100 4713793 http://www.medworm.com/index.php?rid=4713797&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1345 AbstractScreening, isolation and in vitro assays have been used for characterization of antioxidative peptides derived from food proteins, and incompatible deductions of structural characteristics derived from the isolated peptides have been brought forward. However, there is still little information concerning the structure‐activity relationship of antioxidative peptides. QSAR modeling was performed, respectively, on synthetic tripeptides and tetrapeptides related to LLPHH. According to cumulative squared multiple correlation coefficients (R2), cumulative cross‐validation coefficients (Q2) and relative standard deviation for calibration set (RSDc), two credible models for tripeptide and tetrapeptide databases, respectively, have been built with partial least squares (PLS) regression (... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4713797 Tue, 12 Apr 2011 23:00:00 +0100 4713797 http://www.medworm.com/index.php?rid=4692383&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1373 (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4692383 Sat, 09 Apr 2011 03:10:49 +0100 4692383 http://www.medworm.com/index.php?rid=4675813&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1372 AbstractRecently, the rapid emergence of microbial pathogens which are resistant to currently available antibiotics has triggered considerable interest searching for naturally occuring antimicrobial peptides (AMPs). Because AMPs from food organisms are comparatively nontoxic, a number of them are used as sources, purified in new antibiotics. Herein, an antibacterial peptide (heat‐stable KPS‐1) was isolated from Korean pen shell (Atrina pectinata) by the following procedures: solvent‐extraction, heating, ultrafiltration, and RP‐HPLC. The molecular weight of KPS‐1 (4549.1 Da) was revealed by MALDI‐TOF/MS analysis. Interestingly, KPS‐1 inhibited in vitro growth of Gram‐negative bacteria, including Escherichia coli, E. coli O157, Pseudomonas aeruginosa, Enterobacter sakazakii, ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4675813 Thu, 31 Mar 2011 23:00:00 +0100 4675813 http://www.medworm.com/index.php?rid=4669181&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1369 AbstractA class of cationic antimicrobial peptides involved in host defense consists of sequences rich in Lys and Trp. Small peptides, (WK)3 and (KW)3, were designed by the combination of alternating Lys (K) and Trp (W) amino acids, and then their antimicrobial and hemolytic activities were determined. It was noticed that the reversed sequence of (KW)3 showed more activity against all strains than did (WK)3. The non‐hemolytic behavior of (WK)3 is identical to that of the reversed analog of (KW)3. CD spectra revealed that these peptides had an unfolded structure in buffer and EYPC:CH (10:1, w/w), but adopted folded conformation in the presence of EYPE:EYPG (7:3, w/w). The reversed‐(KW)3 peptide caused a higher extent of calcein release from EYPE:EYPG (7:3, w/w), though the activity was ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4669181 Thu, 31 Mar 2011 23:00:00 +0100 4669181 http://www.medworm.com/index.php?rid=4641438&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1366 AbstractPox virus Zinc/Bric‐à‐brac, Tramtrack and Broad (POZ/BTB) is a widespread domain detected in proteins involved in a variety of biological processes. Human genome analyses have unveiled the presence of POZ/BTB domain in a class of proteins (KCTD) whose role as important players in crucial biological processes is emerging. The development of new molecular entities able to interact with these proteins and to modulate their activity is a field of relevant interest. By using molecular modeling and literature mutagenesis analyses, we here designed and characterized a peptide that is able to interact with submicromolar affinities with two different members (KCTD11 and KCTD5) of this family. This finding suggests that the tetrameric KCTD11 and the pentameric KCTD5 are endowed with a s... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4641438 Mon, 28 Mar 2011 16:32:00 +0100 4641438 http://www.medworm.com/index.php?rid=4621381&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1360 AbstractAntimicrobial peptides are major components of the innate self‐defence system and a large number of peptides have been designed to study the mechanism of action. In the present study, a small combinatorial library was designed to study whether the biological activity of Val/Arg‐rich peptides is associated with targeted cell membranes. The peptides were produced by segregating hydrophilic residues on the polar side and hydrophobic residues on the opposite side. The peptides displayed strong antimicrobial activity against Gram‐negative and Gram‐positive bacteria, but weak haemolysis even at a concentration of 256 µM. CD spectra showed that the peptides formed α‐helical‐rich structure in the presence of negatively charged membranes. The tryptophan fluorescence and quench... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4621381 Wed, 23 Mar 2011 01:17:56 +0100 4621381 http://www.medworm.com/index.php?rid=4590115&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1358 AbstractCalcitonin gene‐related peptide (CGRP), a potent dilator of cerebral and dural vasculature, is known to be elevated in plasma and cerebral spinal fluid during migraine attacks. Selective blockade of the CGRP receptor offers the promise of controlling migraine headache more effectively and without the side‐effects associated with the use of triptans. Our efforts to develop a novel, peptide‐based CGRP antagonist focused on the C‐terminal portion of the peptide which is known to bind the receptor but lack agonist properties. Extensive SAR studies of the C‐terminal CGRP (27–37) region identified a novel cyclic structure: Bz‐Val‐Tyr‐cyclo[Cys‐Thr‐Asp‐Val‐Gly‐Pro‐Phe‐Cys]‐Phe‐NH2 (23) with a kb value of 0.126 nM against the cloned human CGRP receptor. ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4590115 Tue, 15 Mar 2011 21:23:38 +0100 4590115 http://www.medworm.com/index.php?rid=4590118&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1363 AbstractAmphibian skin secretion is considered as a rich source of bioactive peptides. The present work describes the successful identification of three novel peptides named brevinin‐1TEa, brevinin‐2TEa and brevinin‐2TEb present in the skin secretion of Indian bronzed frog Hylarana temporalis. The deduced open reading frame encoding the biosynthetic precursor of brevinin‐1TEa consisted of 70 amino acid residues and brevinin‐2TEa and brevinin‐2TEb consisted of 71 and 72 amino acids, respectively. All the three peptides showed higher antimicrobial activity against Gram‐negative than against Gram‐positive bacteria. On the basis of the antibacterial and haemolytic activity, brevinin‐2TEb is the most potent peptide reported in the present study. Further research on these pepti... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4590118 Tue, 15 Mar 2011 00:00:00 +0100 4590118 http://www.medworm.com/index.php?rid=4590117&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1351 AbstractIn the present work, achiral non‐coded amino acids, N‐(Bzl)‐Gly, X1 or X2, were substituted at position 7 of the model B2 receptor antagonist [D‐Arg0, Hyp3, Thi5, 8, D‐Phe7]‐BK. The N‐terminal amino group of the analogues was either free or acylated with 1‐Aca or Aaa. Biological activity of the compounds was assessed in the in vitro rat uterus test and the in vivo rat blood pressure test. The X17 substitution resulted in a decrease in antagonistic potency of the new peptide in both assays. The X27 and N‐(Bzl)‐Gly7 substituted analogues showed weak agonistic properties in the rat uterus test. Interestingly, the latter compound exhibited dual activity in the pressor test, i.e. intrinsic vasodepressor action and at the same time a weak antagonistic effect. Acylatio... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4590117 Tue, 15 Mar 2011 00:00:00 +0100 4590117 http://www.medworm.com/index.php?rid=4590116&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1354 AbstractPeptaibol antibiotics are membrane‐active linear peptides of fungal origin that are characterized by a high population of the Cα‐tetrasubstituted, strongly helicogenic, α‐amino acid, α‐aminoisobutyric acid, an N‐terminal acetyl group, and a C‐terminal 1,2‐amino alcohol. Alamethicins (Alms), among the longest peptaibiotics, are a group of closely sequence‐related peptides composed of 19 amino acid residues. [TOAC1, Glu(OMe)7, 18, 19] Alm and [TOAC16, Glu(OMe)7, 18, 19] Alm are synthetic, nitroxide free‐radical labeled analogs of [Glu(OMe)7, 18, 19] Alm F50/5. In this work, nitroxide to peptide NH proton distance information obtained from paramagnetic relaxation enhancement (PRE) studies on [TOAC1, Glu(OMe)7, 18, 19] Alm is compared with distances derived from an... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4590116 Tue, 15 Mar 2011 00:00:00 +0100 4590116 http://www.medworm.com/index.php?rid=4531317&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1343 AbstractIn order to better understand the mechanisms of action of linear cationic host defense peptides, biophysical and structural investigations of their interactions with membranes and with other biomacromolecules are reviewed. In particular, an extensive overview will be given of the topological studies of magainins in a number of different lipid environments. Furthermore, amphipathic helices have been designed in such a manner to allow the easy control of their membrane alignment. These peptides not only exhibit potent antimicrobial and transfection activities, but their investigation has also provided important insights into mechanistic aspects of their biological functions. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.Biophysical investigations of linear... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4531317 Tue, 01 Mar 2011 00:00:00 +0100 4531317 http://www.medworm.com/index.php?rid=4516577&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1356 AbstractDivalent metal‐ion transporter 1 (DMT1) belongs to a large class of metal‐ion transporters that drive the translocation of a wide range of divalent metal substrates across membranes toward the cytosol with couple of protons. Two highly conserved histidines in the sixth transmembrane domain (TMD6) are essential for metal transport activity in DMT1. In the present study, we determine the high‐resolution structures of three 25‐residue peptides, corresponding to TMD6 of the wildtype DMT1 (the segment 255–279) and its H267A and H272A mutants, in 30% TFE‐d2 aqueous solution by the combined use of circular dichroism (CD) and NMR spectroscopies. The wildtype peptide forms an ‘α‐helix‐extended segment‐α‐helix’ structure with two helices spanning over Gly258–Ala26... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4516577 Fri, 25 Feb 2011 00:14:54 +0100 4516577 http://www.medworm.com/index.php?rid=4516586&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1357 AbstractNPY, PYY and PP constitute the so‐called NPY hormone family, which exert its biological functions in humans through YRs (Y1, Y2, Y4 and Y5). Systematic modulation of YR function became important as this multireceptor/multiligand system is known to mediate various essential physiological key functions and is involved in a variety of major human diseases such as epilepsy, obesity and cancer. As several YRs have been found to be overexpressed on different types of malignant tumors they emerge as promising target in modern drug development. Here, we summarize the current understanding of YRs function and the molecular mechanisms of ligand binding and trafficking. We further address recent advances in YR‐based drug design, the development of promising future drug candidates and nove... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4516586 Thu, 24 Feb 2011 00:00:00 +0100 4516586 http://www.medworm.com/index.php?rid=4516585&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1342 AbstractA series of model peptides in the form of quaternary ammonium salts at the N‐terminus was efficiently prepared by the solid‐phase synthesis. Tandem mass spectrometric analysis of the peptide quaternary ammonium derivatives was shown to provide sequence confirmation and enhanced detection. We designed the 2‐(1,4‐diazabicyclo[2.2.2] octylammonium)acetyl quaternary ammonium group which does not suffer from neutral losses during MS/MS experiments. The presented quaternization of 1,4‐diazabicyclo[2.2.2]octane (DABCO) by iodoacetylated peptides is relatively easy and compatible with standard solid‐phase peptide synthesis. This methodology offers a novel sensitive approach to analyze peptides and other compounds. Copyright © 2011 European Peptide Society and John Wiley & ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4516585 Thu, 24 Feb 2011 00:00:00 +0100 4516585 http://www.medworm.com/index.php?rid=4516584&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1327 AbstractThe development of suitable radioligands for targeting CCK‐2 receptor expressing tumors, such as medullary thyroid carcinoma, is of great clinical interest. In the search for the best CCK‐2R binding peptides, we have synthesized, evaluated and compared the CCK8 peptide (Asp‐Tyr‐Met‐Gly‐Trp‐Met‐Asp‐PheNH2) and two gastrin analogs commonly referred to as MG0 (DGlu‐Glu(5)‐Ala‐Tyr‐Gly‐Trp‐Met‐Asp‐PheNH2) and MG11 (DGlu(1)‐Ala‐Tyr‐Gly‐Trp‐Met‐Asp‐PheNH2). The N‐terminal portion of the three peptide sequences was derivatized by introducing the DTPAGlu or DOTA chelators to allow radiolobeling with 111In(III) and 68Ga(III), respectively. Saturation binding and cellular internalization experiments were performed on A431 cells overex... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4516584 Thu, 24 Feb 2011 00:00:00 +0100 4516584 http://www.medworm.com/index.php?rid=4516583&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1344 AbstractEPR spectroscopy is a technique that specifically detects unpaired electrons. EPR‐sensitive reporter groups (spin labels or spin probes) can be introduced into biological systems via site‐directed spin‐labeling (SDSL). The basic strategy of SDSL involves the introduction of a paramagnetic group at a selected protein site. This is usually accomplished by cysteine‐substitution mutagenesis, followed by covalent modification of the unique sulfydryl group with a selective reagent bearing a nitroxide radical. In this review we briefly describe the theoretical principles of this well‐established approach and illustrate how we successfully applied it to investigate structural transitions in both human pancreatic lipase (HPL), a protein with a well‐defined α/β hydrolase fold, ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4516583 Thu, 24 Feb 2011 00:00:00 +0100 4516583 http://www.medworm.com/index.php?rid=4516582&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1349 AbstractWe previously reported that a novel targeted drug termed hybrid epidermal growth factor receptor (EGFR)‐lytic peptide, made by chemical conjugation of targeted binding peptide and cell‐killing, lytic‐peptide components, has selective cytotoxic activity that allows it to discriminate between normal and cancer cells. In addition, in vivo analysis revealed that this hybrid peptide displays significant antitumor activity in a xenograft model of human breast and pancreatic cancer in mice. Here, we characterized antilytic peptide antibody, which was raised from rabbit serum using the antigen of lytic peptide conjugated with keyhole limpet hemocyanin. It was found that antilytic peptide antibody is specific to the lytic peptide as assessed by both ELISA and surface plasmon resonance... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4516582 Thu, 24 Feb 2011 00:00:00 +0100 4516582 http://www.medworm.com/index.php?rid=4516581&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1347 In this study, we investigated the physico‐chemical characteristics of low‐generation asymmetric peptide dendrimers and their ability to complex pDNA under various conditions. We compared the morphology of our dendriplexes with a commercially available dendrimer and also assessed their cytotoxicity profile. We report that the asymmetric dendrimers form toroids upon complexing with DNA, and that this is dependent upon ionic strength of the complexing solution. Our dendriplexes are also minimally toxic even when very high N:P ratios are employed. (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4516581 Thu, 24 Feb 2011 00:00:00 +0100 4516581 http://www.medworm.com/index.php?rid=4516580&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1346 AbstractThe Z‐molecule is a small, engineered IgG‐binding affinity protein derived from the immunoglobulin‐binding domain B of Staphylococcus aureus protein A. The Z‐domain consists of 58 amino acids forming a well‐defined antiparallel three‐helix structure. Two of the three helices are involved in ligand binding, whereas the third helix provides structural support to the three‐helix bundle. The small size and the stable three‐helix structure are two attractive properties comprised in the Z‐domain, but a further reduction in size of the protein is valuable for several reasons. Reduction in size facilitates synthetic production of any protein‐based molecule, which is beneficial from an economical viewpoint. In addition, a smaller protein is easier to manipulate through c... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4516580 Thu, 24 Feb 2011 00:00:00 +0100 4516580 http://www.medworm.com/index.php?rid=4516579&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1353 AbstractPeptides and proteins are highly dynamic systems, which can adopt more or less stable conformations. The dynamics of these molecules, particularly those on the nanosecond to tens of microsecond time scale, are difficult to assess with conventional techniques. This review summarizes experiments using TTET, a technique that reports on van der Waals contact formation between a triplet donor and acceptor group, and which is sensitive in this time range. TTET allows to directly measure the chain dynamics of unstructured model peptides, i.e. large‐amplitude fluctuations on the nanosecond time scale. Furthermore, contact formation can be used as irreversible probing reaction to study the kinetics of conformational equilibria. This approach enabled us to measure local α‐helix folding ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4516579 Thu, 24 Feb 2011 00:00:00 +0100 4516579 http://www.medworm.com/index.php?rid=4516578&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1355 AbstractEffective surface modification with biocompatible molecules is known to be effective in reducing the life‐threatening risks related to artificial cardiovascular implants. In recent strategies in regenerative medicine, the enhancement and support of natural repair systems at the site of injury by designed biocompatible molecules have succeeded in rapid and effective injury repair. Therefore, such a strategy could also be effective for rapid endothelialization of cardiovascular implants to lower the risk of thrombosis and stenosis. To achieve this enhancement of the natural repair system, a biomimetic molecule that mimics proper cellular organization at the implant location is required. In spite of the fact that many reported peptides have cell‐attracting properties on material s... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4516578 Thu, 24 Feb 2011 00:00:00 +0100 4516578 http://www.medworm.com/index.php?rid=4501037&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1332 AbstractFour diastereomeric‐Leu‐Leu‐Aib‐Leu‐Leu‐Aib‐peptides, Boc‐D‐Leu‐L‐Leu‐Aib‐L‐Leu‐L‐Leu‐Aib‐OMe (1), Boc‐L‐Leu‐D‐Leu‐Aib‐L‐Leu‐L‐Leu‐Aib‐OMe (2), Boc‐L‐Leu‐L‐Leu‐Aib‐D‐Leu‐L‐Leu‐Aib‐OMe (3), and Boc‐L‐Leu‐L‐Leu‐Aib‐L‐Leu‐D‐Leu‐Aib‐OMe (4), were synthesized. The crystals of the four hexapeptides were characterized by X‐ray crystallographic analysis. Two diastereomeric hexapeptides 1 and 2 having D‐Leu(1) or D‐Leu(2) were folded into right‐handed (P) 310‐helical structures, while peptide 3 having D‐Leu(4) was folded into a turn structure nucleated by type III′ and I‐turns, and peptide 4 having D‐Leu(5) was folded into a left‐handed (M) 310‐helical structure. Copyr... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4501037 Mon, 21 Feb 2011 16:04:47 +0100 4501037 http://www.medworm.com/index.php?rid=4494331&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1324 AbstractBacteria employ the SecA motor protein to push unfolded proteins across the cytoplasmic membrane through the SecY protein‐conducting channel complex. The crystal structure of the SecA–SecY complex shows that the intramolecular regulator of ATPase1 (IRA1) SecA domain, made up of two helices and the loop between them, is partly inserted into the SecY conducting channel, with the loop between the helices as the main functional region. A computational analysis suggested that the entire IRA1 domain is structurally autonomous, and was the basis to synthesize peptide analogs of the SecA IRA1 loop region, to the aim of investigating its conformational preferences. Our study indicates that the loop region populates a predominantly flexible state, even in the presence of structuring agen... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4494331 Fri, 18 Feb 2011 23:58:20 +0100 4494331 http://www.medworm.com/index.php?rid=4494332&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1350 AbstractThe increasing resistance of bacteria and fungi to the available antibiotic/antimycotic drugs urges for a search for new anti‐infective compounds with new modes of action. In line of this, natural CAMPs represent promising and attractive candidates. Special attention has been devoted to frog‐skin temporins, because of their short size (10–14 residues long) and their unique features. In particular, temporin‐1Ta has the following properties: (i) it is mainly active on Gram‐positive bacteria; (ii) it can synergize, when combined with temporin‐1Tl, in inhibiting both gram‐negative bacterial growth and the toxic effect of LPS; (iii) it preserves biological activity in the presence of serum; and (iv) it is practically not hemolytic. Rational design of CAMPs represents a str... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4494332 Fri, 18 Feb 2011 00:00:00 +0100 4494332 http://www.medworm.com/index.php?rid=4436281&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1323 In this study, Derringer's desirability function, a multi‐criteria decision‐making method, was applied to determine the best peptide for opioid studies in a single figure‐of‐merit.The penetration of the blood–brain barrier (BBB) determines the biological functionality of neuropeptides in the brain target tissue, and consists of an influx and an efflux component. The metabolic stability in the two concerned tissues, i.e. plasma and brain, are taken into consideration as well. The overall selection of the peptide drug candidate having the highest BBB‐drugability is difficult due to these conflicting responses as well as the different scalings of the four biological parameters under consideration.The highest desirability, representing the best BBB‐drugability, was observed for d... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4436281 Fri, 04 Feb 2011 00:00:00 +0100 4436281 http://www.medworm.com/index.php?rid=4436280&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1333 AbstractNeuroglobin and cellular prion protein (PrPC) are expressed in the nervous system and co‐localized in the retinal ganglion cell layer. Both proteins do not have an unambiguously assigned function, and it was recently reported that PrPC aggregates rapidly in the presence of neuroglobin, whereas it does not aggregate in the presence of myoglobin, another globin with different tissue specificity. Electrostatic complementarity between the unstructured PrPCN‐terminus and neuroglobin has been proposed to mediate this specific interaction. To verifythis hypothesis experimentally, we have used a combined approach of automated docking and molecular dynamics (MD) studies carried out on short stretches of prion protein (PrP) N‐terminus to identify the minimal electrostatically interacti... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4436280 Fri, 04 Feb 2011 00:00:00 +0100 4436280 http://www.medworm.com/index.php?rid=4436279&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1337 AbstractThe relationship between the conformation and biological activity of the peptide allosteric modulator of the interleukin‐1 receptor 101.10 (D‐Arg‐D‐Tyr‐D‐Thr‐D‐Val‐D‐Glu‐D‐Leu‐D‐Ala‐NH2) has been studied using (R)‐ and (S)‐Bgl residues. Twelve Bgl peptides were synthesized using (R)‐ and (S)‐cyclic sulfamidate reagents derived from L‐ and D‐aspartic acid in an optimized Fmoc‐compatible protocol for efficient lactam installment onto the supported peptide resin. Examination of these (R)‐ and (S)‐Bgl 101.10 analogs for their potential to inhibit IL‐1β‐induced thymocyte cell proliferation using a novel fluorescence assay revealed that certain analogs exhibited retained and improved potency relative to the parent peptide 101.10. In li... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4436279 Fri, 04 Feb 2011 00:00:00 +0100 4436279 http://www.medworm.com/index.php?rid=4436278&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1341 AbstractNisin is a peptide bacteriocin, grouped under the category of lantibiotics. It is naturally produced by Lactococcus lactis to eliminate other competing gram‐positive bacteria from its vicinity. Moreover under certain conditions it is reported to be effective against a broad range of gram‐negative bacteria as well. Thus, it has been widely used as a safe food preservative especially in the dairy industry. Because of its wide‐scale consumption, its effect on eukaryotic cells should be of great concern. Here we examine the immunomodulatory efficacy of nisin in vitro. MTT‐based cytotoxicity assay demonstrated nisin's cytotoxicity on human T‐cell lymphoma Jurkat cells, Molt‐4 cells and freshly cultured human lymphocytes at over 200 µM concentration (IC50225 µM). The cell d... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4436278 Fri, 04 Feb 2011 00:00:00 +0100 4436278 http://www.medworm.com/index.php?rid=4436277&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1338 AbstractProtein (lectin/toxin)–glycan interaction can be clinically harmful so that the design of inhibitors has become an aim. Cyclic decapeptides are suited as rigid carriers for carbohydrate derivatives. We herein document the bioactivity of sugar headgroups covalently attached to this carrier for the cases of five proteins, i.e. a potent biohazardous plant agglutinin, a leguminous model lectin and three adhesion/growth‐regulatory human lectins. They represent the different types of topological organization within the galectin family. The relative inhibitory activities of glycoclusters with the three ligands (galactose, lactose and the disaccharide of the Thomsen‐Friedenreich antigen) reflected the affinity of free carbohydrates, hereby excluding an impairment of binding activity ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4436277 Fri, 04 Feb 2011 00:00:00 +0100 4436277 http://www.medworm.com/index.php?rid=4432583&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1328 AbstractObesity is one of the major risk factors for type 2 diabetes, and the development of agents, that can simultaneously achieve glucose control and weight loss, is being actively pursued. Therapies based on peptide mimetics of the gut hormone glucagon‐like peptide 1 (GLP‐1) are rapidly gaining favor, due to their ability to increase insulin secretion in a strictly glucose‐dependent manner, with little or no risk of hypoglycemia, and to their additional benefit of causing a modest, but durable weight loss. Oxyntomodulin (OXM), a 37‐amino acid peptide hormone of the glucagon (GCG) family with dual agonistic activity on both the GLP‐1 (GLP1R) and the GCG (GCGR) receptors, has been shown to reduce food intake and body weight in humans, with a lower incidence of treatment‐assoc... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4432583 Thu, 03 Feb 2011 00:00:00 +0100 4432583 http://www.medworm.com/index.php?rid=4432582&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1330 AbstractA series of linear and monocyclic (with a disulfide bridge only) analogues of trypsin inhibitor SFTI‐1 modified in the P1 and/or P1′ positions were synthesized by the solid‐phase method. In the substrate specificity P1 position, Phe or N‐benzylglycine (Nphe) were introduced, whereas the conserved Ser6 in Bownam‐Birk (BBI) inhibitors was replaced by Hse (L‐homoserine), Nhse [N‐(2‐hydroxyethyl)glycine], Sar, and Ala. Kinetic studies of interaction of the analogues with bovine α‐chymotrypsin have shown that in monocyclic (but not linear) analogues, Hse and Nhse are tolerated to afford potent inhibitors. This is the first evidence that the absolutely conserved Ser present in the inhibitor's P1′ position can be successfully replaced by a synthetic derivative. Copyri... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4432582 Thu, 03 Feb 2011 00:00:00 +0100 4432582 http://www.medworm.com/index.php?rid=4436276&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1340 AbstractCell‐penetrating peptides (CPPs) are cationic oligopeptides able to translocate across biological membranes without perturbing them, while antimicrobial peptides (AMPs) kill bacteria mainly by disrupting their membranes. The two peptide classes share several characteristics (charge, amphipathicity, helicity, and length), and therefore the molecular properties discriminating between the two different bioactivities are not clear. Pep‐1‐K (KKTWWKTWWTKWSQPKKKRKV) is a new AMP derived from the widely studied CPP Pep‐1 (KETWWETWWTEWSQPKKKRKV), or ‘Chariot’, known for its ability to carry large cargoes across biological membranes. Pep‐1‐K was obtained from Pep‐1 by substituting the three Glu residues with Lys, to increase its cationic character. Previous studies showed t... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4436276 Tue, 01 Feb 2011 00:00:00 +0100 4436276 http://www.medworm.com/index.php?rid=4432581&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1336 AbstractSide‐chain assisted ligation is an auxiliary‐mediated ligation strategy in which a thiol bearing cyclohexane or cyclopentane is attached to the side‐chain of Asp, Glu, Ser or Thr to function in a similar manner to Cys in a native chemical ligation. Following the ligation step, the auxiliary is removed, without product isolation, under alkaline conditions. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.Side‐chain assisted ligation is an auxiliary‐mediated ligation strategy in which a thiol bearing cyclohexane or cyclopentane is attached to the side‐chain of Asp, Glu, Ser or Thr to function in a similar manner to Cys in a native chemical ligation. Following the ligation step, the auxiliary is removed, without product isolation, under alkaline co... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4432581 Tue, 01 Feb 2011 00:00:00 +0100 4432581 http://www.medworm.com/index.php?rid=4370158&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1322 AbstractROS, continuously produced in cells, can reversibly or irreversibly oxidize proteins, lipids, and DNA. At the protein level, cysteine, methionine, tryptophan, and tyrosine residues are particularly prone to oxidation. Here, we describe the solid phase synthesis of peptides containing four different oxidation products of tryptophan residues that can be formed by oxidation in proteins in vitro and in vivo: 5‐HTP, Oia, Kyn, and NFK. First, we synthesized Oia and NFK by selective oxidation of tryptophan and then protected the ‐amino group of both amino acids, and the commercially available 5‐HTP, with Fmoc‐succinimide. High yields of Fmoc‐Kyn were obtained by acid hydrolysis of Fmoc‐NFK. All four Fmoc derivatives were successfully incorporated, at high yields, into three di... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4370158 Wed, 19 Jan 2011 22:29:31 +0100 4370158 http://www.medworm.com/index.php?rid=4370159&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1316 AbstractPeptides isolated from natural fonts are the object of several studies aimed at finding new molecules possessing antibacterial activity. We focused our studies on peptides originally isolated from the Royal Jelly, the jelleins and on some analogs having a UV reporter at the N‐ or C‐terminus. We found that jelleins are mainly active against gram‐positive bacteria; interestingly, they act in synergy with peptides belonging to the family of temporins such as temporin A and temporin B against Staphylococcus aureus A170 and Listeria monocytogenes. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.Peptides isolated from the Royal Jelly, the Jelleins, are mainly active against gram positive bacteria; interestingly they act in synergy with peptides belonging t... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4370159 Wed, 19 Jan 2011 00:00:00 +0100 4370159 http://www.medworm.com/index.php?rid=4342226&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1335 AbstractAmphiphilic β‐sheet nanotapes based on the self‐assembly of 9mer and 7mer de novo designed β‐strand peptides were studied in the dilute regime. The hydrophobic face of the tapes consisted predominantly of aliphatic (leucine) side chains, while the hydrophilic tape face contained polar side chains (glutamine, arginine and glutamic acid). Both peptides underwent a transition from a monomeric random coil to a self‐assembled β‐sheet tape upon increase of peptide concentration in aqueous solutions. P9‐6 exhibited lower critical concentration (c*) for self‐assembly and thus higher propensity for self‐assembly in water, compared to the shorter P7‐6. At neutral pH where there was little net charge per peptide, self‐assembly was favoured compared to low pH in which th... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4342226 Thu, 13 Jan 2011 23:44:56 +0100 4342226 http://www.medworm.com/index.php?rid=4342225&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1348 (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4342225 Thu, 13 Jan 2011 23:44:54 +0100 4342225 http://www.medworm.com/index.php?rid=4336913&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1307 AbstractThe use of lanthanides in preference to radioisotopes as probes for various biological assays has gained enormous popularity. The introduction of lanthanide chelates to peptides/proteins can be carried out either in solution using a commercially available labelling kit or by solid‐phase peptide synthesis using an appropriate lanthanide chelate. Herein, a detailed protocol for the latter is provided for the labelling of peptides or small proteins with diethylenetriamine‐N, N, N″, N″‐tetra‐tert‐butyl acetate‐N′‐acetic acid (DTPA) chelate or other similar chelates on a solid support using a chimeric insulin‐like peptide composed of human insulin‐like peptide 5 (INSL5) A‐chain and relaxin‐3 B‐chain as a model peptide. Copyright © 2011 European Peptide Soc... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4336913 Tue, 11 Jan 2011 00:00:00 +0100 4336913 http://www.medworm.com/index.php?rid=4336912&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1313 AbstractMaurotoxin (MTX) is a 34‐residue toxin that was isolated initially from the venom of the scorpion Scorpio maurus palmatus. Unlike the other toxins of the α‐KTx6 family (Pi1, Pi4, Pi7, and HsTx1), MTX exhibits a unique disulfide bridge organization of the type C1C5, C2C6, C3C4, and C7C8 (instead of the conventional C1C5, C2C6, C3C7, and C4C8, herein referred to as Pi1‐like) that does not prevent its folding along the classic α/β scaffold of scorpion toxins. MTXPi1 is an MTX variant with a conventional pattern of disulfide bridging without any primary structure alteration of the toxin. Here, using MTX and/or MTXPi1 as models, we investigated how the type of folding influences toxin recognition of the Shaker B potassium channel. Amino acid residues of ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4336912 Tue, 11 Jan 2011 00:00:00 +0100 4336912 http://www.medworm.com/index.php?rid=4336911&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1298 AbstractNitration of tyrosine residues has been shown to be an important oxidative modification in proteins and has been suggested to play a role in several diseases such as atherosclerosis, asthma, lung and neurodegenerative diseases. Detection of nitrated proteins has been mainly based on the use of nitrotyrosine‐specific antibodies. In contrast, only a small number of nitration sites in proteins have been unequivocally identified by MS. We have used a monoclonal 3‐NT‐specific antibody, and have synthesized a series of tyrosine‐nitrated peptides of prostacyclin synthase (PCS) in which a single specific nitration site at Tyr‐430 had been previously identified upon reaction with peroxynitrite17. The determination of antibody‐binding affinity and specificity of PCS peptides nitr... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4336911 Sat, 01 Jan 2011 00:00:00 +0100 4336911 http://www.medworm.com/index.php?rid=4304651&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1321 AbstractThis work presents a computational strategy to model flexible molecules tethered to a metallic rigid surface. The method is based on a previously developed procedure for inert surfaces, in which peptide–surface interactions were not considered. This procedure is able to generate uncorrelated relaxed microstructures at the atomistic level of systems containing relatively high densities of peptides tethered to the surface. The reliability of the strategy has been tested by simulating CREKA (Cys‐Arg‐Glu‐Lys‐Ala), a short linear pentapeptide that recognizes clotted plasma proteins and selectively homes to tumors, covalently tethered to a gold surface, results being compared with those obtained when the surface was represented as inert. The results indicate that the whole conf... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4304651 Sat, 01 Jan 2011 00:00:00 +0100 4304651 http://www.medworm.com/index.php?rid=4292898&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1335 AbstractAmphiphilic β‐sheet nanotapes based on the self‐assembly of 9mer and 7mer de novo designed β‐strand peptides were studied in the dilute regime. The hydrophobic face of the tapes consisted predominantly of aliphatic (leucine) side chains, while the hydrophilic tape face contained polar side chains (glutamine, arginine and glutamic acid). Both peptides underwent a transition from a monomeric random coil to a self‐assembled β‐sheet tape upon increase of peptide concentration in aqueous solutions. P9‐6 exhibited lower critical concentration (c*) for self‐assembly and thus higher propensity for self‐assembly in water, compared to the shorter P7‐6. At neutral pH where there was little net charge per peptide, self‐assembly was favoured compared to low pH in which th... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4292898 Wed, 29 Dec 2010 02:12:47 +0100 4292898 http://www.medworm.com/index.php?rid=4292902&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1326 We report in this review on a wide research of PNM intrinsic physical properties, their electronic and optical properties related to QC effect, unique SHG, piezoelectricity and ferroelectric spontaneous polarization observed in PNT due to their asymmetric structure. We also describe PNM wettability phenomenon based on their nanoporous structure and its influence on electrochemical properties in PNM.The new bottom‐up large scale technology of PNT physical vapor deposition and patterning combined with found physical effects at nanoscale, developed by us, opens the avenue for emerging nanotechnology applications of PNM in novel fields of nanophotonics, nanopiezotronics and energy storage devices. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.Two sorts of vapor de... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4292902 Tue, 28 Dec 2010 00:00:00 +0100 4292902 http://www.medworm.com/index.php?rid=4292901&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1329 AbstractThe photocurrent generation properties of mono‐ and bi‐component peptide‐based self‐assembled monolayers (SAMs) immobilized on a gold surface were studied by electrochemical and spectroscopic techniques. The peptides investigated comprised almost exclusively Cα‐tetrasubstituted α‐amino acids. These non‐coded residues, because of their unique conformational properties, forced the peptide backbone to attain a helical conformation, as confirmed by X‐ray crystal structure and CD determinations in solution. The peptide helical structure promoted the formation of a stable SAM on the gold surface, characterized by an electric macrodipole directed from the C(δ−) to the N(δ+) terminus, that remarkably affected the electron transfer (ET) process through the peptide chai... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4292901 Tue, 28 Dec 2010 00:00:00 +0100 4292901 http://www.medworm.com/index.php?rid=4292900&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1331 AbstractWe used the principles governing the selectivity and stability of coiled‐coil segments to design and experimentally test a set of four pairs of parallel coiled‐coil‐forming peptides composed of four heptad repeats. The design was based on maximizing the difference in stability between desired pairs and the most stable unwanted combinations using N‐terminal helix initiator residues, favorable combinations of the electrostatic and hydrophobic interaction motifs and negative design motif based on burial of asparagine residues. Experimental analysis of all 36 pair combinations among the eight peptides was performed by circular dichroism (CD). On the basis of CD spectra, each peptide formed a high level of α‐helical structure exclusively in combination with its designed pepti... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4292900 Tue, 28 Dec 2010 00:00:00 +0100 4292900 http://www.medworm.com/index.php?rid=4292899&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1334 This study presents synthesis and self‐assembly of a mannosylated peptide in aqueous medium. Turbidimetric assay with Concanavalin A (Con A), a mannose binding protein, was conducted to confirm the presence of hydrophilic mannose group on the exterior surface of self‐assembled structures. DNA encapsulation in these soft structures was achieved by ultrasonication of soft spherical structures in the presence of plasmid DNA. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.This paper describes a novel glycopeptide conjugate which self‐assembles to give spherical structures, with a unique ability of encapsulating DNA, upon ultrasonication. (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4292899 Tue, 28 Dec 2010 00:00:00 +0100 4292899 http://www.medworm.com/index.php?rid=4271885&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1339 AbstractAβ16–22 (Ac‐KLVFFAE‐NH2) is one of the shortest amyloid fibril‐forming sequences identified in β‐amyloid peptide. At neutral pH, the peptide forms fibrils in the concentration range of 0.2–2.0 mM after ≥ 10 days of incubation. Structures of the fibrils proposed based on solid‐state NMR and MD simulations studies suggest antiparallel arrangement of β‐strands and aromatic interactions between the Phe residues. In an effort to examine the role of aromatic interactions between two Phe residues in Aβ16–22, we have studied the self‐assembly of Aβ16–22 (AβFF) and two of its variants, Ac‐KLVFWAE‐NH2 (AβFW) and Ac‐KLVWFAE‐NH2 (AβWF). The peptides were dissolved in methanol (MeOH) at a concentration of 1 mM and in water (AβFW and AβWF, 1 mM; AβFF, 3... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4271885 Mon, 20 Dec 2010 09:24:25 +0100 4271885 http://www.medworm.com/index.php?rid=4212631&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1315 AbstractConsiderable advances in materials science are expected via the use of selected or designed peptides to recognize material, control their growth, or to assemble them into elaborate novel devices. Identifying specific peptides for a number of technologically useful materials has been the challenge of many research groups in recent years. This can be accomplished by using affinity‐based bio‐panning methods such as phage display technologies. In this work, a combinatorial library including billions of clones of genetically engineered M13 bacteriophage was used to select peptides that could recognize improved indium nitride (InN) semiconductor (SC) material. Several rounds of biopanning were necessary to select the phage with the higher affinity from the low variant library. The DN... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4212631 Wed, 01 Dec 2010 00:00:00 +0100 4212631 http://www.medworm.com/index.php?rid=4212634&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1320 AbstractThe influenza virus, major surface glycoprotein hemagglutinin (HA) is one of the principal targets for the development of protective immunity. Aiming at contributing to the development of a vaccine that remains the first choice for prophylactic intervention, a reconstituted model of HA, mimicking its antigenic properties was designed, synthesized and tested in mice for the induction of protective immunity. Four helper T lymphocyte [HTL (T1, T3, T7 and T8)] and four cytotoxic lymphocyte [CTL (T2, T4, T5 and T6)] epitopes were coupled in two copies each to an artificial carrier, SOC4, which was formed by the repeating tripeptide Lys‐Aib‐Gly. The helical conformation of the SOC4‐conjugates preserves the initial topology of the attached epitopes, which is critical for their immun... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4212634 Tue, 30 Nov 2010 00:00:00 +0100 4212634 http://www.medworm.com/index.php?rid=4212633&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1319 AbstractMany antimicrobial agents that target bacteria are cationic and can interact with the anionic lipid components that are exposed on the bacterial membrane. Bacteria vary widely in the nature of the major lipid components that are in the cell membrane. Those bacteria with both anionic as well as zwitterionic or neutral lipids can be induced to form domains in the presence of antimicrobial peptides possessing several cationic charges. This segregation of anionic and zwitterionic lipids into domains can result in the arrest of cell growth or in cell death. Such agents are generally more toxic to Gram‐negative bacteria, than to Gram‐positive ones. These findings emphasize the importance of the lipid composition of bacterial membranes in determining the susceptibility of the organism... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4212633 Tue, 30 Nov 2010 00:00:00 +0100 4212633 http://www.medworm.com/index.php?rid=4212632&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1317 This study reveals that single amino acid differences at positions 68 & 128 in GLP‐1R influence selectivity for ligand action. (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4212632 Tue, 30 Nov 2010 00:00:00 +0100 4212632 http://www.medworm.com/index.php?rid=4212635&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1310 AbstractDendrimeric platforms such as MAPs can be synthesized either entirely by solid‐phase methods (SPPS, direct approach) or by conjugation in solution of preformed, SPPS‐made building blocks (indirect approach). Although MAPs and MAP‐like constructs have been extensively and successfully used for various biological (mainly immunological) applications, experimental reports are most often lacking in chemical detail about their preparation and characterization. Here, we provide complete accounts of the synthesis and analytical documentation of MAPs and similar dendrimers by either all‐SPPS (direct) or chemoselective thioether ligation (indirect) methods. We have chosen as model epitopes a 24‐residue sequence of the ectodomain of protein M2 from influenza virus (M2e), which is fo... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4212635 Mon, 29 Nov 2010 00:00:00 +0100 4212635 http://www.medworm.com/index.php?rid=4196094&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1325 AbstractThe membrane proximal external region (MPER) of gp41 abuts the viral membrane at the base of HIV‐1 envelope glycoprotein spikes. The MPER is highly conserved and is rich in Trp and other lipophilic residues. The MPER is also required for the infection of host cells by HIV‐1 and is the target of the broadly neutralizing antibodies, 4E10, 2F5, and Z13e1. These neutralizing antibodies are valuable tools for understanding relevant conformations of the MPER and for studying HIV‐1 neutralization, but multiple approaches used to elicit MPER binding antibodies with similar neutralization properties have failed. Here we report our efforts to mimic the MPER using linear as well as constrained peptides. Unnatural amino acids were also introduced into the core epitope of 4E10 to probe re... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4196094 Wed, 24 Nov 2010 14:31:38 +0100 4196094 http://www.medworm.com/index.php?rid=4196091&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1318 AbstractA family of His‐rich peptides has been shown to complex DNA and efficiently deliver these nucleic acids into eukaryotic cells. Therefore, these nanoscale complexes have potential applications in gene therapy. Here, we review a number of spectroscopic and biophysical investigations aimed at characterizing the supramolecular interactions of the peptides with the nucleic acids and when overcoming the membrane barriers of the cell. Furthermore, solid‐state NMR distance measurements for the first time reveal close interatomic distances between the amino acid side chains and the DNA phosphates within the transfection complex. A recent study indicates that the peptides are also potent transfectants of siRNAs and they could thereby be of potential interest for gene silencing therapies ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4196091 Wed, 24 Nov 2010 14:30:43 +0100 4196091 http://www.medworm.com/index.php?rid=4196092&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1311 AbstractIn order to investigate the relationship between the primary structure of Orpotrin, a vasoactive peptide previously isolated from the freshwater stingray Potamotrygon gr. orbignyi, and its microcirculatory effects, three Orpotrin analogs were synthesized. The analogs have a truncated N‐terminal with a His residue deletion and two substituted amino acid residues, where one Nle is substituted for one internal Lys residue and the third analog has a substitution of a Pro for an Ala (Orp‐desH1, Orp‐Nle and Orp‐Pro/Ala, respectively). Only Orp‐desH1 could induce a lower vasoconstriction effect compared with the natural Orpotrin, indicating that besides the N‐terminal, the positive charge of Lys and the Pro residues located at the center of the amino acid chain is crucial for ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4196092 Tue, 23 Nov 2010 00:00:00 +0100 4196092 http://www.medworm.com/index.php?rid=4196093&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1312 AbstractIdentification of substrate specificity of kinases is crucial to understand the roles of the kinases in cellular signal transduction pathways. Here, we present an approach applicable for the discovery of substrate specificity of Ser/Thr kinases. The method, which is named as the ‘high‐throughput phosphorylation profiling (HTPP)’ method was developed on the basis of a fully randomized one‐bead one‐compound (OBOC) combinatorial ladder type peptide library and MALDI‐TOF MS. The OBOC ladder peptide library was constructed by the ‘split and pool’ method on a HiCore resin. The peptide library sequence was Ac‐Ala‐X‐X‐X‐Ser‐X‐X‐Ala‐BEBE‐PLL resin. The substrate specificity of murine PKA (cAMP‐dependent protein kinase A) and yeast Yak1 kinase was identi... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4196093 Mon, 22 Nov 2010 00:00:00 +0100 4196093 http://www.medworm.com/index.php?rid=4104564&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1299 Abstract (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4104564 Tue, 26 Oct 2010 09:50:02 +0100 4104564 http://www.medworm.com/index.php?rid=4011300&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1296 Abstract (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=4011300 Wed, 29 Sep 2010 20:09:25 +0100 4011300 http://www.medworm.com/index.php?rid=3983134&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1290 Abstract (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3983134 Mon, 20 Sep 2010 09:58:40 +0100 3983134 http://www.medworm.com/index.php?rid=3975908&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1286 Abstract (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3975908 Fri, 17 Sep 2010 08:32:42 +0100 3975908 http://www.medworm.com/index.php?rid=3972322&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1291 (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3972322 Thu, 16 Sep 2010 08:32:18 +0100 3972322 http://www.medworm.com/index.php?rid=3841775&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1269 Abstract (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3841775 Mon, 09 Aug 2010 12:47:09 +0100 3841775 http://www.medworm.com/index.php?rid=3841774&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1267 Abstract (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3841774 Mon, 09 Aug 2010 12:47:09 +0100 3841774 http://www.medworm.com/index.php?rid=3841773&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1266 Abstract (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3841773 Mon, 09 Aug 2010 12:47:08 +0100 3841773 http://www.medworm.com/index.php?rid=3841772&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1265 Abstract (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3841772 Mon, 09 Aug 2010 12:47:05 +0100 3841772 http://www.medworm.com/index.php?rid=3841771&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1255 Abstract (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3841771 Mon, 09 Aug 2010 12:47:04 +0100 3841771 http://www.medworm.com/index.php?rid=3841770&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1271 Abstract (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3841770 Mon, 09 Aug 2010 12:47:03 +0100 3841770 http://www.medworm.com/index.php?rid=3841763&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1268 Abstract (Source: Journal of Peptide Science) Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3841763 Mon, 09 Aug 2010 12:46:59 +0100 3841763 http://www.medworm.com/index.php?rid=3771506&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1271 We study the complex formation of a peptide [beta]A[beta]AKLVFF, previously developed by our group, with A[beta](1-42) in aqueous solution. Circular dichroism spectroscopy is used to probe the interactions between [beta]A[beta]AKLVFF and A[beta](1-42), and to study the secondary structure of the species in solution. Thioflavin T fluorescence spectroscopy shows that the population of fibers is higher in [beta]A[beta]AKLVFF/A[beta](1-42) mixtures compared to pure A[beta](1-42) solutions. TEM and cryo-TEM demonstrate that co-incubation of [beta]A[beta]AKLVFF with A[beta](1-42) causes the formation of extended dense networks of branched fibrils, very different from the straight fibrils observed for A[beta](1-42) alone. Neurotoxicity assays show that although [beta]A[beta]AKLVFF alters the fibr... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3771506 Tue, 20 Jul 2010 23:00:00 +0100 3771506 http://www.medworm.com/index.php?rid=3771508&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1268 We investigated the mechanism of candidacidal action of a Lys/Leu-rich [alpha]-helical model antimicrobial peptide (K9L8W) and its diastereomeric peptide (D9-K9L8W) composed of D,L-amino acids. K9L8W killed completely Candida albicans within 30 min, but D9-K9L8W killed only 72% of C. albicans even after 100 min. Tryptophan fluorescence spectroscopy indicated that the fungal cell selectivity of D9-K9L8W is closely correlated with a selective interaction with the negatively charged PC/PE/PI/ergosterol (5:2.5:2.5:1, w/w/w/w) phospholipids, which mimic the outer leaflet of the plasma membrane of C. albicans. K9L8W was able to induce almost 100% calcein leakage from PC/PE/PI/ergosterol (5:2.5:2.5:1, w/w/w/w) liposomes at a peptide:lipid molar ratio of 1:16, whereas D9-K9L8W caused only 25% dye ... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3771508 Mon, 19 Jul 2010 23:00:00 +0100 3771508 http://www.medworm.com/index.php?rid=3771507&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1270 In this study, cationic peptides containing Aib were prepared to evaluate the availability as an antimicrobial agent, especially against representative pathogenic bacteria. Among them, BRBA20, consisting of five repeated Aib-Arg-Aib-Ala sequences, showed strong antibacterial activity against both Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Additionally, growth of Serratia marcescens and multidrug-resistant Pseudomonas aeruginosa, known as proteases-secreting pathogenic bacteria, were also completely inhibited by BRBA20 under 20 µg/ml peptide concentrations. Our results suggested availabilities of Aib-derived amphiphilicity and protease resistance in the design of artificial antimicrobial peptides. Comparing BRBA20 with BKBA20, it was al... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3771507 Mon, 19 Jul 2010 23:00:00 +0100 3771507 http://www.medworm.com/index.php?rid=3771510&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1267 Dehydrobutyrine is the most naturally occurring dehydroamino acid. It is also the simplest dehydroamino acid having the geometrical isomers E/Z. To investigate its conformational properties, a theoretical analysis was performed on N-acetyl-[alpha],[beta]-dehydrobutyrine N[prime]-methylamides, Ac-(E)-[Delta]Abu-NHMe and Ac-(Z)-[Delta]Abu-NHMe, as well as the dehydrovaline derivative Ac-[Delta]Val-NHMe. The [phis], [psi] potential energy surfaces and the localised conformers were calculated at the B3LYP/6-311 + + G(d,p) level of theory both in vacuo and with inclusion of the solvent (chloroform, water) effect (SCRF method). The X-ray crystal structures of Ac-(Z)-[Delta]Abu-NHMe and Ac-[Delta]Val-NHMe were determined at 85 and 100 K, respectively. The solid-state conformational preferences fo... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3771510 Sun, 18 Jul 2010 23:00:00 +0100 3771510 http://www.medworm.com/index.php?rid=3771509&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1266 The neuropeptides galanin (GAL), neuropeptide Y (NPY) or neurotensin (NT) exhibit anticonvulsant activities mediated by their respective receptors in the brain. To transform these peptides into potential neurotherapeutics, their systemic bioavailability and metabolic stability must be improved. Our recent studies with GAL analogs suggested that an introduction of lipoamino acids in the context of oligo-Lys residues (lipidization-cationization motif) significantly increases their penetration into the brain, yielding potent antiepileptic compounds. Here, we describe an extension of this strategy to NPY and NT. Rationally designed analogs of NPY and NT containing the lipidization-cationization motif were chemically synthesized and their physicochemical and pharmacological properties were char... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3771509 Sun, 18 Jul 2010 23:00:00 +0100 3771509 http://www.medworm.com/index.php?rid=3761035&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1264 was designed and prepared by reverse proteolysis in partial organic solvent of a single-chain precursor expressed in yeast. The precursor contains two loops to bridge the two chains of native insulin. The cyclisation method uses Achromobacter lyticus protease and should be generally applicable to proteins with C-terminal lysine and proximal N-terminal. The presence of the ring-closing bond and the native insulin disulfide patterns were documented by LC-MS peptide maps. The cyclic insulin was shown to be inert towards degradation by CPY, but was somewhat labile towards chymotrypsin. Intravenous administration of the cyclic insulin to Wistar rats showed the compounds to be equipotent to HI despite much lower insulin receptor affinity. Copyright © 2010 European Peptide Society and John Wile... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3761035 Fri, 16 Jul 2010 23:00:00 +0100 3761035 http://www.medworm.com/index.php?rid=3753220&cid=s_33780_60_f&fid=33780&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fpsc.1269 Precise microwave heating has emerged as a valuable method to aid solid-phase peptide synthesis (SPPS). New methods and reliable protocols, as well as their embodiment in automated instruments, are required to fully use this potential. Here we describe a new automated robotic instrument for SPPS with microwave heating, report protocols for its reliable use and report the application to the synthesis of long sequences, including the [beta]-amyloid 1-42 peptide. The instrument is built around a valve-free robot originally developed for parallel peptide synthesis, where the robotic arm transports reagents instead of pumping reagents via valves. This is the first example of an 'X-Y' robotic microwave-assisted synthesizer developed for the assembly of long peptides. Although the instrument main... Journal of Peptide Science journals http://www.medworm.com/rss/comments.php?id=3753220 Wed, 14 Jul 2010 23:00:00 +0100 3753220