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Advances in engineering of fluorescent proteins and photoactivatable proteins with red emission.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monomeric fluorescent proteins of different colors are widely used to study behavior and targeting of proteins in living cells. Fluorescent proteins that irreversibly change their spectral properties in response to light irradiation of a specific wavelength, or photoactivate, have become increasingly popular to image intracellular dynamics and superresolution protein localization. Until recently, however, no optimized monomeric red fluorescent proteins and red photoactivatable proteins have been available. Furthermore, monomeric fluorescent proteins, which change emission from blue to red simply with time, so-called fl...
Source: Current Opinion in Chemical Biology - November 13, 2009 Category: Biochemistry Authors: Piatkevich KD, Verkhusha VV Tags: Curr Opin Chem Biol Source Type: journals

Functionalized (129)Xe contrast agents for magnetic resonance imaging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The concept of 'xenon biosensor' for magnetic resonance imaging (MRI) was first proposed by a Berkeley team in 2001, with evidence that hyperpolarized (129)Xe bound to a biotin-labeled cryptophane can detect streptavidin at much lower concentrations (nM-muM) than is typical for contrast-enhanced MRI experiments. (129)Xe biosensors have undergone many recent developments to address challenges in molecular imaging. For example, cryptophanes that exhibit 10-fold higher xenon affinity with distinct (129)Xe magnetic resonance spectra have been synthesized. Also relevant are dendrimeric cryptophane assemblies and inorganic z...
Source: Current Opinion in Chemical Biology - November 12, 2009 Category: Biochemistry Authors: Taratula O, Dmochowski IJ Tags: Curr Opin Chem Biol Source Type: journals

Current concepts on hyperpolarized molecules in MRI.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hyperpolarization provides a strong enhancement of the MR signal and allows the acquisition of images from nuclei other than protons. Besides vascular imaging and perfusion studies the use of hyperpolarized molecules has allowed the visualization of real-time substrate uptake and metabolism in vivo. Metabolic imaging is an outstanding field of research that aims at providing the clinicians with the possibility of interrogating real-time complex metabolic pathways that give a direct insight into the cellular state and activity. PMID: 19913452 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - November 11, 2009 Category: Biochemistry Authors: Viale A, Aime S Tags: Curr Opin Chem Biol Source Type: journals

Designs and applications of fluorescent protein-based biosensors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genetically encoded biosensors allow the noninvasive imaging of specific biochemical or biorecognition processes with the preservation of subcellular spatial and temporal information. Aequorea green fluorescent protein (FP) and its engineered variants are a critical component of genetically encoded biosensors, as they serve to provide a 'read-out' of the biorecognition event under investigation. The family of FP-based biosensors includes a diverse array of designs that utilize various photophysical characteristics of the FPs. In this review, we will discuss these designs and their read-outs through reviewing some of th...
Source: Current Opinion in Chemical Biology - November 11, 2009 Category: Biochemistry Authors: Ibraheem A, Campbell RE Tags: Curr Opin Chem Biol Source Type: journals

Fluorescent protein-based biosensors: resolving spatiotemporal dynamics of signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cellular processes are orchestrated by the precise coordination and regulation of molecular events in the cell. Fluorescent protein-based biosensors coupled with live-cell imaging have enabled the visualization of these events in real time and helped shape some of the current concepts of signal transduction, such as spatial compartmentation. The quantitative information produced by these tools has been incorporated into mathematical models that are capable of predicting highly complex and dynamic behaviors of cellular signaling networks, thus providing a systems level understanding of how pathways interact to produce a...
Source: Current Opinion in Chemical Biology - November 10, 2009 Category: Biochemistry Authors: Dipilato LM, Zhang J Tags: Curr Opin Chem Biol Source Type: journals

Mitochondrial-targeted fluorescent probes for reactive oxygen species.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
As the primary consumers of oxygen within all aerobic organisms, mitochondria are a major source of cellular reactive oxygen species (ROS) derived from the in vivo chemistry of oxygen metabolism. Mitochondrial ROS have been traditionally implicated in aging and in a variety of pathologies, including cancer, neurodegeneration, and diabetes, but recent studies also link controlled mitochondrial ROS fluxes to cell regulation and signaling events. Progress in the development of mitochondrial-targeted fluorescent small-molecule indicators that detect specific ROS with high selectivity offers a promising approach for interro...
Source: Current Opinion in Chemical Biology - November 10, 2009 Category: Biochemistry Authors: Dickinson BC, Srikun D, Chang CJ Tags: Curr Opin Chem Biol Source Type: journals

Super-resolution optical microscopy: multiple choices.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The recent invention of super-resolution optical microscopy enables the visualization of fine features in biological samples with unprecedented clarity. It creates numerous opportunities in biology because vast amount of previously obscured subcellular processes now can be directly observed. Rapid development in this field in the past two years offers many imaging modalities that address different needs but they also complicates the choice of the 'perfect' method for answering a specific question. Here I will briefly describe the principles of super-resolution optical microscopy techniques and then focus on comparing t...
Source: Current Opinion in Chemical Biology - November 6, 2009 Category: Biochemistry Authors: Huang B Tags: Curr Opin Chem Biol Source Type: journals

Progress in single-molecule spectroscopy in cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Time-dependent single-molecule spectroscopy allows the direct observation of molecular processes in real time, capturing transient and stochastic events that cannot be detected using conventional ensemble-averaged methods. It offers a promising approach to uncovering the physical and chemical transformations underlying cellular responses. Recent advances in the probe development, specific labeling strategies, and spectroscopy instrumentation suggest the feasibility of monitoring a single molecular machine's actions inside a living cell. PMID: 19896891 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - November 5, 2009 Category: Biochemistry Authors: Yang H Tags: Curr Opin Chem Biol Source Type: journals

Fluorescent small-molecule probes of biochemistry at the plasma membrane.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The function of cellular membranes remains a critical area of study. Advances in molecular biology and biochemistry have helped to define the plasma membrane as a dynamic and heterogeneous structure. Probes capable of resolving molecular interactions and biochemical changes within the membrane are becoming a necessary tool for cell biology studies. We review current examples that apply small molecule fluorophores to label either lipids or proteins to study the plasma membrane. We discuss probes of the lipid environment itself, as well as labeling strategies for membrane proteins and membrane receptors. PMID: 198964...
Source: Current Opinion in Chemical Biology - November 4, 2009 Category: Biochemistry Authors: Cairo CW, Key JA, Sadek CM Tags: Curr Opin Chem Biol Source Type: journals

Development of responsive lanthanide probes for cellular applications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Useful probes of the intracellular environment are required for a wide range of bioactive species including metal ions, oxyanions and pH. These probes need to be targeted to specific organelles (mitochondria, nucleus and lysosomes) in order to allow direct observation of the changes in these regions. Critical probe design features for luminescent lanthanide complexes are defined, together with a review of published sub-cellular localisation profiles. Cell uptake by macropinocytosis has been demonstrated for a wide range of probes and the importance of minimising perturbation of cellular homeostasis emphasised, so that ...
Source: Current Opinion in Chemical Biology - October 31, 2009 Category: Biochemistry Authors: New EJ, Parker D, Smith DG, Walton JW Tags: Curr Opin Chem Biol Source Type: journals

Modular strategies for PET imaging agents.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In recent years, modular and simplified chemical and biological strategies have been developed for the synthesis and implementation of positron emission tomography (PET) radiotracers. New developments in bioconjugation and synthetic methodologies, in combination with advances in macromolecular delivery systems and gene-expression imaging, reflect a need to reduce radiosynthesis burden in order to accelerate imaging agent development. These new approaches, which are often mindful of existing infrastructure and available resources, are anticipated to provide a more approachable entry point for researchers interested in u...
Source: Current Opinion in Chemical Biology - October 30, 2009 Category: Biochemistry Authors: Hooker JM Tags: Curr Opin Chem Biol Source Type: journals

Near-infrared fluorescence: application to in vivo molecular imaging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Molecular imaging often relies on the use of targeted and activatable reporters to quantitate and visualize targets, biological processes, and cells in vivo. The use of optical probes with near-infrared fluorescence allows for improved photon penetration through tissue and minimizes the effects of tissue autofluorescence. There are several parameters that define the effectiveness of imaging agents in vivo. These factors include probe targeting, activation, pharmacokinetics, biocompatibility, and photophysics. Recent advances in our understanding of these variables as they pertain to the application of optical reporters...
Source: Current Opinion in Chemical Biology - October 29, 2009 Category: Biochemistry Authors: Hilderbrand SA, Weissleder R Tags: Curr Opin Chem Biol Source Type: journals

Non-natural nucleic acids for synthetic biology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genetic manipulation is an important facet of synthetic biology but can be complicated by undesired nuclease degradation. Incorporating non-natural nucleic acids into a gene could convey resistance to nucleases and promote expression. The compatibility of non-natural nucleosides with polymerases is reviewed with a focus on results from the past two years. Details are provided about how the different systems could be useful in synthetic biology. PMID: 19879178 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - October 28, 2009 Category: Biochemistry Authors: Appella DH Tags: Curr Opin Chem Biol Source Type: journals

Model systems: how chemical biologists study RNA.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ribonucleic acids are structurally and functionally sophisticated biomolecules and the use of models, frequently truncated or modified sequences representing functional domains of the natural systems, is essential to their exploration. Functional noncoding RNAs such as miRNAs, riboswitches, and, in particular, ribozymes, have changed the view of RNA's role in biology and its catalytic potential. The well-known truncated hammerhead model has recently been refined and new data provide a clearer molecular picture of the elements responsible for its catalytic power. A model for the spliceosome, a massive and highly intrica...
Source: Current Opinion in Chemical Biology - October 28, 2009 Category: Biochemistry Authors: Rios AC, Tor Y Tags: Curr Opin Chem Biol Source Type: journals

Peptide membranes in chemical evolution.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Simple surfactants achieve remarkable long-range order in aqueous environments. This organizing potential is seen most dramatically in biological membranes where phospholipid assemblies both define cell boundaries and provide a ubiquitous structural scaffold for controlling cellular chemistry. Here we consider simple peptides that also spontaneously assemble into exceptionally ordered scaffolds, and review early data suggesting that these structures maintain the functional diversity of proteins. We argue that such scaffolds can achieve the required molecular order and catalytic agility for the emergence of chemical evo...
Source: Current Opinion in Chemical Biology - October 28, 2009 Category: Biochemistry Authors: Childers WS, Ni R, Mehta AK, Lynn DG Tags: Curr Opin Chem Biol Source Type: journals

Model substrates for studies of cell mobility.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cells do not live in static surroundings, they exist in highly evolving dynamic environments. During cell adhesion and migration, cells adapt and communicate to their environment by numerous methods ranging from differentiation, gene expression, growth, and apoptosis. How and when cells determine to adhere, polarize, and migrate is important to a number of fundamental biological processes such as wound healing, metastasis, inflammation, and development. In order to elucidate the spatial and temporal mechanisms of these important complex processes on a molecular basis, several research groups have generated model substr...
Source: Current Opinion in Chemical Biology - October 26, 2009 Category: Biochemistry Authors: Yousaf MN Tags: Curr Opin Chem Biol Source Type: journals

Light activation as a method of regulating and studying gene expression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recently, several advances have been made in the activation and deactivation of gene expression using light. These developments are based on the application of small molecule inducers of gene expression, antisense- or RNA interference-mediated gene silencing, and the photochemical control of proteins regulating gene function. The majority of the examples employ a classical 'caging technology', through the chemical installation of a light-removable protecting group on the biological molecule (small molecule, oligonucleotide, or protein) of interest and rendering it inactive. UV light irradiation then removes the caging ...
Source: Current Opinion in Chemical Biology - October 24, 2009 Category: Biochemistry Authors: Deiters A Tags: Curr Opin Chem Biol Source Type: journals

Mimicking nature: from fundamentals to applications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19854670 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - October 23, 2009 Category: Biochemistry Authors: Waters ML, Appella DH Tags: Curr Opin Chem Biol Source Type: journals

Carbohydrate arrays: recent developments in fabrication and detection methods with applications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Carbohydrate arrays can provide facile analyses of carbohydrate-binding proteins, antibodies in serum, and enzyme activities with minimal quantities of sugar samples. Recent developments in detection methods for carbohydrate arrays, especially surface plasmon resonance (SPR) and mass spectrometry, have enabled not only qualitative but in some cases quantitative data analysis in a variety of multivalent display formats. These advancements make diagnostic tools based on carbohydrate arrays more promising for infectious disease detection, cancer monitoring, and vaccine development. PMID: 19853494 [PubMed - as supplied...
Source: Current Opinion in Chemical Biology - October 22, 2009 Category: Biochemistry Authors: Song EH, Pohl NL Tags: Curr Opin Chem Biol Source Type: journals

The promise and challenge of '-omic' approaches.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19853495 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - October 21, 2009 Category: Biochemistry Authors: Macbeath G, Saghatelian A Tags: Curr Opin Chem Biol Source Type: journals

Integrated omics approaches in plant systems biology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Understanding cellular metabolic systems is vital not only for determining the function of enzymatic genes, but also for elucidating the coordination among various metabolic pathways. In this context, high-throughput experiments can provide us with essential, albeit only partial information. Integration of metabolite profiling with other multiple 'omics' data (e.g. transcript profiling), is required to reconstruct complex networks that characterize the phenotypes in the cell. Here, we review recent approaches to integrate multiple omics data in higher plants. We especially focus on metabolomics data management, normali...
Source: Current Opinion in Chemical Biology - October 15, 2009 Category: Biochemistry Authors: Fukushima A, Kusano M, Redestig H, Arita M, Saito K Tags: Curr Opin Chem Biol Source Type: journals

Design of membrane proteins: toward functional systems.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Over the years, membrane-soluble peptides have provided a convenient model system to investigate the folding and assembly of integral membrane proteins. Recent advances in experimental and computational methods are now being translated into the design of functional membrane proteins. Applications include artificial modulators of membrane protein function, inhibitors of protein-protein interactions, and redox membrane proteins. PMID: 19828358 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - October 12, 2009 Category: Biochemistry Authors: Ghirlanda G Tags: Curr Opin Chem Biol Source Type: journals

Non-genetic cell-to-cell variability and the consequences for pharmacology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent advances in single-cell assays have focused attention on the fact that even members of a genetically identical group of cells or organisms in identical environments can exhibit variability in drug sensitivity, cellular response, and phenotype. Underlying much of this variability is stochasticity in gene expression, which can produce unique proteomes even in genetically identical cells. Here we discuss the consequences of non-genetic cell-to-cell variability in the cellular response to drugs and its potential impact for the treatment of human disease. PMID: 19833543 [PubMed - as supplied by publisher] (Source...
Source: Current Opinion in Chemical Biology - October 12, 2009 Category: Biochemistry Authors: Niepel M, Spencer SL, Sorger PK Tags: Curr Opin Chem Biol Source Type: journals

Recent progress in chemical and chemoenzymatic synthesis of carbohydrates.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The important roles that carbohydrates play in biological processes and their potential application in diagnosis, therapeutics, and vaccine development have made them attractive synthetic targets. Despite ongoing challenges, tremendous progresses have been made in recent years for the synthesis of carbohydrates. The chemical glycosylation methods have become more sophisticated and the synthesis of oligosaccharides has become more predictable. Simplified one-pot glycosylation strategy and automated synthesis are increasingly used to obtain biologically important glycans. On the other hand, chemoenzymatic synthesis conti...
Source: Current Opinion in Chemical Biology - October 12, 2009 Category: Biochemistry Authors: Muthana S, Cao H, Chen X Tags: Curr Opin Chem Biol Source Type: journals

Connecting synthetic chemistry decisions to cell and genome biology using small-molecule phenotypic profiling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Discovering small-molecule modulators for thousands of gene products requires multiple stages of biological testing, specificity evaluation, and chemical optimization. Many cellular profiling methods, including cellular sensitivity, gene expression, and cellular imaging, have emerged as methods to assess the functional consequences of biological perturbations. Cellular profiling methods applied to small-molecule science provide opportunities to use complex phenotypic information to prioritize and optimize small-molecule structures simultaneously against multiple biological endpoints. As throughput increases and cost de...
Source: Current Opinion in Chemical Biology - October 10, 2009 Category: Biochemistry Authors: Wagner BK, Clemons PA Tags: Curr Opin Chem Biol Source Type: journals

Chemical approaches toward understanding glycan-mediated protein quality control.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
High-mannose-type oligosaccharides, which are cotranslationally introduced to nascent polypeptides during N-glycosylation, play critical roles in protein quality control. Involved in this process are a number of intracellular carbohydrate-recognizing proteins or carbohydrate-processing enzymes, including calnexin/calreticulin, malectin, glucosidase I (G-I) and II (G-II), UDP-glucose:glycoprotein glucosyltransferase (UGGT), cargo receptors (VIP36, ERGL, and ERGIC-53), ER 1,2-mannosidase I, ER degradation-enhancing alpha-mannosidase-like proteins (EDEMs) and ubiquitin ligase. Although all these proteins seem to recognize...
Source: Current Opinion in Chemical Biology - October 9, 2009 Category: Biochemistry Authors: Takeda Y, Totani K, Matsuo I, Ito Y Tags: Curr Opin Chem Biol Source Type: journals

Inorganic biomimetic nanostructures.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Supramolecular structures modeled after biological systems (DNA and enzymes) are being developed to simultaneously mimic natural biological functions including catalysis, information storage, and self-assembly and to engineer novel electronic and magnetic properties. Structural mimics of nucleic acids containing multiple metal-coordinating ligands, and comprising natural and artificial bases or completely synthetic systems, create stable double-stranded structures with new electronic, spectroscopic, and magnetic properties. Supramolecular inorganic mimics of enzymatic function, including metallonucleases and metallopro...
Source: Current Opinion in Chemical Biology - October 6, 2009 Category: Biochemistry Authors: Levine LA, Williams ME Tags: Curr Opin Chem Biol Source Type: journals

Perspectives of targeted mass spectrometry for protein biomarker verification.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article reviews the current, targeted proteomic strategies that are capable of quantifying biomarker candidates at concentration ranges where biomarkers are expected in plasma (i.e. at the ng/ml level). In addition, a workflow is presented that allows the fast and definitive generation of targeted mass spectrometry-based assays for most biomarker candidate proteins. These assays are stored in publicly accessible databases and have the potential to greatly impact the throughput of biomarker verification studies. PMID: 19818677 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - October 6, 2009 Category: Biochemistry Authors: Hüttenhain R, Malmström J, Picotti P, Aebersold R Tags: Curr Opin Chem Biol Source Type: journals

Recent advances in mycobacterial cell wall glycan biosynthesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The cell wall of mycobacteria, including the causative agents of the human diseases tuberculosis (Mycobacterium tuberculosis) and leprosy (M. leprae), is composed of an array of carbohydrate-containing molecules. These glycoconjugates are assembled by glycosyltransferases (GTs) that work in tandem through pathways that are only now beginning to be fully understood. Given the essentiality of cell wall glycans to mycobacterial viability, these enzymes represent novel targets for drug action. Summarized here are recent genetic and biochemical studies leading to the identification and characterization of mycobacterial GTs....
Source: Current Opinion in Chemical Biology - October 2, 2009 Category: Biochemistry Authors: Tam PH, Lowary TL Tags: Curr Opin Chem Biol Source Type: journals

Biopolymers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19800837 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - September 30, 2009 Category: Biochemistry Authors: Guo Z Tags: Curr Opin Chem Biol Source Type: journals

Recent progress and applications in glycosaminoglycan and heparin research.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Heparin, the focus of this review, is a crucially important anticoagulant drug produced from animal sources, which was contaminated last year leading to a number of adverse side effects, some resulting in death. Heparin is a highly acidic polysaccharide and a member of a family of biopolymers called glycosaminoglycans. The structure and activities of heparin are detailed along with recent advances in heparin structural analysis and biological evaluation. Current state-of-the-art chemical and chemoenzymatic synthesis of heparin and new approaches for its metabolic engineering are described. New technologies, including m...
Source: Current Opinion in Chemical Biology - September 22, 2009 Category: Biochemistry Authors: Laremore TN, Zhang F, Dordick JS, Liu J, Linhardt RJ Tags: Curr Opin Chem Biol Source Type: journals

Glycomics and disease markers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glycomics is the comprehensive study of all glycans expressed in biological systems. The biosynthesis of glycan relies on a number of highly competitive processes involving glycosyl transferases. Glycosylation is therefore highly sensitive to the biochemical environment and has been implicated in many diseases including cancer. Recently, interest in profiling the glycome has increased owing to the potential of glycans for disease markers. In this regard, mass spectrometry is emerging as a powerful technique for profiling the glycome. Global glycan profiling of human serum based on mass spectrometry has already led to s...
Source: Current Opinion in Chemical Biology - September 20, 2009 Category: Biochemistry Authors: An HJ, Kronewitter SR, de Leoz ML, Lebrilla CB Tags: Curr Opin Chem Biol Source Type: journals

Directed mass spectrometry: towards hypothesis-driven proteomics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
To date, the vast majority of the proteomic data sets collected by mass spectrometry (MS) have been generated by nondirected methods, whereby the identified precursor ions are stochastically selected for sequencing from complex sample mixtures. Recently, new MS approaches have been developed in which the mass spectrometer is directed to select and fragment sets of precursor ions that represent the most informative peptides in a sample mixture. These directed MS methods have shown superior performance for the fast, sensitive, and highly reproducible generation of consistent data sets at low redundancy. In this manuscrip...
Source: Current Opinion in Chemical Biology - September 20, 2009 Category: Biochemistry Authors: Schmidt A, Claassen M, Aebersold R Tags: Curr Opin Chem Biol Source Type: journals

Enzymatic transglycosylation for glycoconjugate synthesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Remarkable advances have been made in recent years in exploiting the transglycosylation activity of glycosidases and glycosynthase mutants for oligosaccharide and glycoconjugate synthesis. New glycosynthases were generated from retaining glycosidases, inverting glycosidases, and those that proceed in a mechanism of substrate-assisted catalysis. Directed evolution coupled with elegant screening methods has led to the discovery of an expanding number of glycosynthase mutants that show improved catalytic activity and/or altered substrate specificity. In particular, enzymatic transglycosylation strategy has been recently e...
Source: Current Opinion in Chemical Biology - September 16, 2009 Category: Biochemistry Authors: Wang LX, Huang W Tags: Curr Opin Chem Biol Source Type: journals

Recent development in carbohydrate-based cancer vaccines.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tumor-associated carbohydrate antigens (TACAs) are important molecular markers on the cancer cell surface, useful for the development of therapeutic cancer vaccines or cancer immunotherapies. However, because of their poor immunogenicity and/or immunotolerance, most TACAs fail to induce T cell-mediated immunity that is critical for cancer therapy. This review summarizes the recent effort to overcome this problem via constructing TACA conjugates with improved immunogenicity, such as by covalently coupling TACAs to proper carrier molecules to form clustered or multi-epitopic conjugate vaccines, coupling TACAs to a T cell...
Source: Current Opinion in Chemical Biology - September 15, 2009 Category: Biochemistry Authors: Guo Z, Wang Q Tags: Curr Opin Chem Biol Source Type: journals

Recent highlights in systems chemistry.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Systems chemistry deals with complex systems which exhibit properties that emerge only through the collective behavior of its components. Selected examples of recent advances in this field include the spontaneous synchronization of oscillating reactions, new methodology for developing chemical systems that exhibit reaction-diffusion patterns, chiral symmetry breaking in dispersions of crystals, the emergence of self-replicators from molecular networks, and self-assembly under kinetic control. PMID: 19748306 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - September 9, 2009 Category: Biochemistry Authors: Peyralans JJ, Otto S Tags: Curr Opin Chem Biol Source Type: journals

Hexosamine analogs: from metabolic glycoengineering to drug discovery.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article describes the versatility of metabolic glycoengineering, which is a prime example of 'chemical glycobiology,' and gives an overview of its capability to endow complex carbohydrates in living cells and animals with interesting (and useful!) functionalities. Then an overview is provided describing how acylated monosaccharides, a class of molecules originally intended to be efficiently-used, membrane-permeable metabolic intermediates, have led to the discovery that a subset of these compounds (e.g. tributanoylated hexosamines) display unanticipated 'scaffold-dependent' activities; this finding establishes these m...
Source: Current Opinion in Chemical Biology - September 8, 2009 Category: Biochemistry Authors: Wang Z, Du J, Che PL, Meledeo MA, Yarema KJ Tags: Curr Opin Chem Biol Source Type: journals

Lipidomics: a mass spectrometry based systems level analysis of cellular lipids.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lipidomics is a logical outcome of the history and traditions of lipid biochemistry and advances in mass spectrometry are at the heart of a renaissance in understanding the roles of lipids in cellular functions. Our desire to understand the complexity of lipids in biology has led to new techniques that allow us to identify over 1000 phospholipids in mammalian cell types and tissues. Improvements in chromatographic separation and mass spectrometry have positioned us to determine not only the lipid composition (i.e. parts list) of cells and tissues, but also address questions regarding lipid substrates and products that ...
Source: Current Opinion in Chemical Biology - September 7, 2009 Category: Biochemistry Authors: Ivanova PT, Milne SB, Myers DS, Brown HA Tags: Curr Opin Chem Biol Source Type: journals

Identifying druggable disease-modifying gene products.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Many disease genes encode proteins that are difficult to target directly using small molecule drugs. Improvements in libraries based on synthetic compounds, natural products, and other types of molecules may ultimately allow some challenging proteins to be successfully targeted; however, these developments alone are unlikely to be sufficient. A complementary strategy exploits the functional interconnectivity of intracellular networks to find druggable targets lying upstream, downstream, or in parallel to a disease-causing gene, where modulation can influence the disease process indirectly. These targets can be selected...
Source: Current Opinion in Chemical Biology - September 6, 2009 Category: Biochemistry Authors: Dixon SJ, Stockwell BR Tags: Curr Opin Chem Biol Source Type: journals

From single molecules to whole organisms: the evolving field of mechanistic enzymology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19740697 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - September 6, 2009 Category: Biochemistry Authors: Drennan CL, Jarrett JT Tags: Curr Opin Chem Biol Source Type: journals

Post-translation modifications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19733502 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - September 2, 2009 Category: Biochemistry Authors: Lebrilla CB, Mahal LK Tags: Curr Opin Chem Biol Source Type: journals

Methods for the proteomic identification of protease substrates.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Proteolysis is a key regulatory post-translational modification in diverse cellular processes including programed cell death, immune function, and development. Tracking proteolytic events has become a focus of researchers assessing the downstream consequences of protease activation. In this review we summarize unbiased methods for identifying protease substrates and tracking the extent of cleavage, a field termed 'degradomics'. These include one-dimensional and two-dimensional gel-based methods for identifying protease substrates, N-terminal peptide identification methods for simultaneously identifying substrates and c...
Source: Current Opinion in Chemical Biology - August 31, 2009 Category: Biochemistry Authors: Agard NJ, Wells JA Tags: Curr Opin Chem Biol Source Type: journals

Profiling protein tyrosine phosphatase activity with mechanistic probes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The protein tyrosine phosphatases are a family of enzymes that play critical roles in regulating physiological processes including cellular signaling, growth, differentiation, and the immune response. As new roles emerge for these enzymes in human disease, interest in understanding their mechanism of regulation and function has increased correspondingly. The recent development of mechanism-based probes for phosphatase activity has paved the way for detailed studies of tyrosine phosphatase activity and regulation in both physiological and pathological cellular signaling. PMID: 19716756 [PubMed - as supplied by publi...
Source: Current Opinion in Chemical Biology - August 26, 2009 Category: Biochemistry Authors: Krishnamurthy D, Barrios AM Tags: Curr Opin Chem Biol Source Type: journals

Sweet tasting chips: microarray-based analysis of glycans.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glycosylation, a ubiquitous post-translational modification of proteins and lipids that generates enormous functional diversity, is rapidly gaining attention in the postgenomic era. The systematic study of glycans, that is glycomics, has been driven by the development of new analytical tools well suited to the inherent complexities of carbohydrate analysis, such as lectin-based microarray technologies. Recent work has demonstrated the utility of these analytical tools for glycomics in both clinical and research settings, for example identifying novel biomarkers associated with disease progression or studying HIV-1 exit...
Source: Current Opinion in Chemical Biology - August 25, 2009 Category: Biochemistry Authors: Hsu KL, Mahal LK Tags: Curr Opin Chem Biol Source Type: journals

Determination of glycosylation sites and site-specific heterogeneity in glycoproteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glycosylation is one of the most common post-translational modifications (PTMs) of proteins. At least 50% of human proteins are glycosylated with some estimates being as high as 70%. Glycoprotein analysis requires determining both the sites of glycosylation as well as the glycan structures associated with each site. Recent advances have led to the development of new analytical methods that employ mass spectrometry extensively making it possible to obtain the glycosylation site and the site microheterogeneity. These tools will be important for the eventual development of glycoproteomics. PMID: 19700364 [PubMed - as ...
Source: Current Opinion in Chemical Biology - August 20, 2009 Category: Biochemistry Authors: An HJ, Froehlich JW, Lebrilla CB Tags: Curr Opin Chem Biol Source Type: journals

Structures and mechanisms of the mycothiol biosynthetic enzymes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the past decade, the genes encoding all four enzymes responsible for the biosynthesis of mycothiol in Mycobacterium tuberculosis have been identified. Orthologs of each of these have been stably expressed and structurally characterized. The chemical mechanisms of all the four have also been studied. Because of the unique phylogenetic distribution of mycothiol, and the enzymes responsible for its biosynthesis, these enzymes represent interesting potential targets for antimycobacterial agents. PMID: 19699138 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - August 18, 2009 Category: Biochemistry Authors: Fan F, Vetting MW, Frantom PA, Blanchard JS Tags: Curr Opin Chem Biol Source Type: journals

Chemical tools for understanding protein lipidation in eukaryotes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lipidation of proteins is an important mechanism to regulate protein trafficking and activity in cell and tissues. The targeting of proteins to membranes by lipidation plays key roles in many physiological processes and when not regulated properly can lead to cancer and neurological disorders. Dissecting the precise roles of protein lipidation in physiology and disease is a major challenge. Recent advances in chemical biology have now enabled the semisynthesis of lipidated proteins for fundamental biochemical and cellular studies. In addition, new chemical reporters of protein lipidation have improved the detection and...
Source: Current Opinion in Chemical Biology - August 18, 2009 Category: Biochemistry Authors: Charron G, Wilson J, Hang HC Tags: Curr Opin Chem Biol Source Type: journals

Fluorescent biosensors for real-time tracking of post-translational modification dynamics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dynamic post-translational modifications (PTMs) regulate and diversify protein properties and cellular behaviors. Real-time monitoring of these modifications has been made possible with biosensors based on fluorescent proteins (FPs) and fluorescence resonance energy transfer (FRET), which can provide spatiotemporal information of PTMs with little perturbation to the cellular environment. In this review, we highlight available fluorescent biosensors applicable to detect PTMs in living cells and how they have shed light on biological questions that have been difficult to address otherwise. In addition, we also provide di...
Source: Current Opinion in Chemical Biology - August 11, 2009 Category: Biochemistry Authors: Aye-Han NN, Ni Q, Zhang J Tags: Curr Opin Chem Biol Source Type: journals

The tinker, tailor, soldier in intracellular B(12) trafficking.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The recognition of eight discrete genetic complementation groups among patients with inherited cobalamin disorders provided early insights into the complexity of a cofactor-processing pathway that supports only two known B(12)-dependent enzymes in mammals. With the identification of all eight genes now completed, biochemical interrogations of their functions have started and are providing novel insights into a trafficking pathway involving porters that tinker with and tailor the active cofactor forms and editors that ensure the fidelity of the cofactor loading process. The principles of sequestration and escorted deliv...
Source: Current Opinion in Chemical Biology - August 6, 2009 Category: Biochemistry Authors: Banerjee R, Gherasim C, Padovani D Tags: Curr Opin Chem Biol Source Type: journals

Dissecting protein function and signaling using protein microarrays.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although many methods exist to study the recognition and signaling properties of proteins in isolation, it remains a challenge to perform these investigations on a system-wide or proteome-wide scale and within the context of biological complexity. Protein microarray technology provides a powerful tool to assess the selectivity of protein-protein interactions in high-throughput and to quantify the abundances and post-translational modification states of many different proteins in complex mixtures. Here, we provide an overview of the various applications of protein microarray technology and compare the strengths and tech...
Source: Current Opinion in Chemical Biology - August 3, 2009 Category: Biochemistry Authors: Wolf-Yadlin A, Sevecka M, Macbeath G Tags: Curr Opin Chem Biol Source Type: journals