Download or read book A Non directed Strategy to Activity based Protein Profiling written by Gregory Charles Adam and published by . This book was released on 2003 with total page 492 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteomics research requires methods to characterize the expression and function of proteins in complex mixtures. Toward this end, chemical probes that incorporate known affinity labeling agents have facilitated the activity-based profiling of certain enzyme families. This thesis describes the development of a non-directed, or combinatorial, strategy to accelerate the discovery of proteomics probes for enzyme classes lacking cognate affinity labels. Members of a probe library bearing a sulfonate ester chemotype were screened against complex proteomes for activity-dependent protein reactivities. Most proteins showed preferential labeling with specific members of the library, indicating that the varied binding group element was at least in part specifying the proteome reactivity of the probes. Biotin-tagged or trifunctional probes were applied to the affinity isolation of these reactivities which were subsequently identified by mass spectrometry methods as sulfonate targets from nine mechanistically distinct enzyme classes. Surprisingly, none of these enzymes represented targets of previously described proteomics probes. The identification of the amino acid residue(s) labeled in several of these enzyme targets confirmed that sulfonate esters function as active site-directed probes and are capable of profiling enzymes by modification of a variety of active site residues. The sulfonate library was also used to identify several targets, including glutathione S -transferase GSTO 1-1, tissue transglutaminase, and platelet-type phosphofructokinase, that were found to be upregulated in invasive human breast cancer cell lines. These results indicate that activity-based probes compatible with whole-proteome analysis can be developed for numerous enzyme classes and applied to identify novel protein markers of discrete pathological states.
Download or read book Activity Based Protein Profiling written by Stephan A. Sieber and published by Springer Science & Business Media. This book was released on 2012-02-21 with total page 175 pages. Available in PDF, EPUB and Kindle. Book excerpt: ABPP Methodology: Introduction and Overview, by Matthew B. Nodwell und Stephan A. Sieber Activity-Based Protein Profiling for Natural Product Target Discovery, by Joanna Krysiak und Rolf Breinbauer Photoaffinity Labeling in Activity-Based Protein Profiling, by Paul P. Geurink, Laurette M. Prely, Gijs A. van der Marel, Rainer Bischoff und Herman S. Overkleeft Application of Activity-Based Protein Profiling to the Study of Microbial Pathogenesis, by William P. Heal und Edward W. Tate Functional Analysis of Protein Targets by Metabolomic Approaches, by Yun-Gon Kim und Alan Saghatelian
Download or read book Activity Based Protein Profiling written by Benjamin F. Cravatt and published by Springer. This book was released on 2019-01-25 with total page 417 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides a collection of contemporary perspectives on using activity-based protein profiling (ABPP) for biological discoveries in protein science, microbiology, and immunology. A common theme throughout is the special utility of ABPP to interrogate protein function and small-molecule interactions on a global scale in native biological systems. Each chapter showcases distinct advantages of ABPP applied to diverse protein classes and biological systems. As such, the book offers readers valuable insights into the basic principles of ABPP technology and how to apply this approach to biological questions ranging from the study of post-translational modifications to targeting bacterial effectors in host-pathogen interactions.
Download or read book Activity Based Protein Profiling written by Stephan A. Sieber and published by Springer Science & Business Media. This book was released on 2012-02-22 with total page 175 pages. Available in PDF, EPUB and Kindle. Book excerpt: ABPP Methodology: Introduction and Overview, by Matthew B. Nodwell und Stephan A. Sieber Activity-Based Protein Profiling for Natural Product Target Discovery, by Joanna Krysiak und Rolf Breinbauer Photoaffinity Labeling in Activity-Based Protein Profiling, by Paul P. Geurink, Laurette M. Prely, Gijs A. van der Marel, Rainer Bischoff und Herman S. Overkleeft Application of Activity-Based Protein Profiling to the Study of Microbial Pathogenesis, by William P. Heal und Edward W. Tate Functional Analysis of Protein Targets by Metabolomic Approaches, by Yun-Gon Kim und Alan Saghatelian
Download or read book Mass Spectrometry Based Chemical Proteomics written by W. Andy Tao and published by John Wiley & Sons. This book was released on 2019-07-10 with total page 448 pages. Available in PDF, EPUB and Kindle. Book excerpt: PROVIDES STRATEGIES AND CONCEPTS FOR UNDERSTANDING CHEMICAL PROTEOMICS, AND ANALYZING PROTEIN FUNCTIONS, MODIFICATIONS, AND INTERACTIONS—EMPHASIZING MASS SPECTROMETRY THROUGHOUT Covering mass spectrometry for chemical proteomics, this book helps readers understand analytical strategies behind protein functions, their modifications and interactions, and applications in drug discovery. It provides a basic overview and presents concepts in chemical proteomics through three angles: Strategies, Technical Advances, and Applications. Chapters cover those many technical advances and applications in drug discovery, from target identification to validation and potential treatments. The first section of Mass Spectrometry-Based Chemical Proteomics starts by reviewing basic methods and recent advances in mass spectrometry for proteomics, including shotgun proteomics, quantitative proteomics, and data analyses. The next section covers a variety of techniques and strategies coupling chemical probes to MS-based proteomics to provide functional insights into the proteome. In the last section, it focuses on using chemical strategies to study protein post-translational modifications and high-order structures. Summarizes chemical proteomics, up-to-date concepts, analysis, and target validation Covers fundamentals and strategies, including the profiling of enzyme activities and protein-drug interactions Explains technical advances in the field and describes on shotgun proteomics, quantitative proteomics, and corresponding methods of software and database usage for proteomics Includes a wide variety of applications in drug discovery, from kinase inhibitors and intracellular drug targets to the chemoproteomics analysis of natural products Addresses an important tool in small molecule drug discovery, appealing to both academia and the pharmaceutical industry Mass Spectrometry-Based Chemical Proteomics is an excellent source of information for readers in both academia and industry in a variety of fields, including pharmaceutical sciences, drug discovery, molecular biology, bioinformatics, and analytical sciences.
Download or read book Novel Cofactors written by Judith P. Klinman and published by Gulf Professional Publishing. This book was released on 2001-10-05 with total page 502 pages. Available in PDF, EPUB and Kindle. Book excerpt: A cofactor is a component part of many enzymes and functions by uniting with another molecule in order to become active. The use of cofactors to supplement the native amino acids of a protein is essential to maintain the chemical capabilities necessary for organisms to survive. This volume focuses on the significant advances of the past decade in identifying and describing new cofactors--either small molecules or those derived posttranslationally.
Download or read book Chemical Proteomics written by Gerard Drewes and published by Humana Press. This book was released on 2011-11-08 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The multidisciplinary science of chemical proteomics studies how small molecules of synthetic or natural origin bind to proteins and modulate their function. In Chemical Proteomics: Methods and Protocols, expert researchers in the field provide key techniques to investigate chemical proteomics focusing on analytical strategies, how probes are generated, techniques for the discovery of small molecule targets and the probing of target function, and small molecule ligand and drug discovery. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Chemical Proteomics : Methods and Protocols seeks to provide methodologies that will contribute to a wider application of chemical proteomics methods in biochemical and cell biological laboratories.
Download or read book Activity Based Protein Profiling written by Stephan A. Sieber and published by Springer. This book was released on 2012-02-28 with total page 168 pages. Available in PDF, EPUB and Kindle. Book excerpt: ABPP Methodology: Introduction and Overview, by Matthew B. Nodwell und Stephan A. Sieber Activity-Based Protein Profiling for Natural Product Target Discovery, by Joanna Krysiak und Rolf Breinbauer Photoaffinity Labeling in Activity-Based Protein Profiling, by Paul P. Geurink, Laurette M. Prely, Gijs A. van der Marel, Rainer Bischoff und Herman S. Overkleeft Application of Activity-Based Protein Profiling to the Study of Microbial Pathogenesis, by William P. Heal und Edward W. Tate Functional Analysis of Protein Targets by Metabolomic Approaches, by Yun-Gon Kim und Alan Saghatelian
Download or read book Designing Multi Target Drugs written by J. Richard Morphy and published by Royal Society of Chemistry. This book was released on 2012-03-28 with total page 395 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multi-target drug discovery (MTDD) is an emerging area of increasing interest to the drug discovery community. Drugs that modulate several targets have the potential for an improved balance of efficacy and safety compared to single targets agents. Although there are a number of marketed drugs that are thought to derive their therapeutic benefit by virtue of interacting with multiple targets, the majority of these were discovered accidentally. Written by world renowned experts, this is the first book to gather together knowledge and experiences of the rational discovery of multi-target drugs. It describes the current state of the art, the achievements and the challenges of the field and importantly the lessons learned by researchers to date and their application to future MTDD.
Download or read book Marine Biomedicine written by Bill J. Baker and published by CRC Press. This book was released on 2015-11-05 with total page 612 pages. Available in PDF, EPUB and Kindle. Book excerpt: Marine Biomedicine: From Beach to Bedside assesses current efforts in marine biomedicine and evaluates the implications of recent advances on the future of the field.Richly illustrated in full color to enhance reader comprehension, the book covers four sections. The first one addresses the technology that has recently been brought to bear on the st
Download or read book Enzyme Discovery and Characterization by Proteome Reactivity Profiling written by Katherine T. Barglow and published by . This book was released on 2008 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteomics aims to identify new markers and targets for the diagnosis and treatment of human disease. To realize this goal, methods and reagents are needed to profile proteins based on their functional properties, rather than mere abundance. To this end, activity-based protein profiling (ABPP), the use of active site-directed chemical probes to monitor enzyme function in complex biological systems, is emerging as a powerful post-genomic tool. Herein, we describe a strategy for the generation of libraries of non-directed activity-based probes, and their use for both enzyme discovery and characterization. We first synthesized and evaluated a structurally diverse library of probes consisting of a dipeptide binding group, an [alpha]-chloroacetamide ([alpha]-CA) electrophile, and a rhodamine/biotin tag, which labeled a wide variety of enzyme classes. We then utilized quantitative screening of probe-proteome reactions coupled with bioinformatic analysis to select a suite of probes that exhibit complementary protein reactivity profiles. This optimal probe set was applied to discover several known and novel enzyme activities differentially expressed in lean and obese ( ob/ob ) mice, and over the course of adipogenesis. Interestingly, one of these enzymes, hydroxypyruvate reductase (HPR), which may contribute to gluconeogenesis, was 6-fold upregulated in activity but not expression in obese over lean livers, and appears to be regulated in lean livers by a protein-protein interaction that blocks the active site. We next expanded our probe library and generated a second optimal set designed to label a large percentage of the targets of all possible dipeptide [alpha]-CA probes, and also allow for the systematic SAR study of probe-protein reactivity. From this set, we discovered probes for the nitrilase family of enzymes, a poorly-understood, highly conserved family of C-N hydrolases. For the nitrilase ureidopropionase-[beta], the probes, discovered de novo from screening, acted as close substrate mimics, implying that probe labeling profiles may offer insight into substrate selectivity for uncharacterized enzymes. Towards that end, we solved the structure of the nitrilase enzyme mouse Nit2 at 1.4Å resolution. Through a combination of probe labeling, mutagenesis, and molecular modeling, we propose a model of probe (and, by extension) substrate binding into the active site of this uncharacterized enzyme.
Download or read book New and Emerging Proteomic Techniques written by Dobrin Nedelkov and published by Springer Science & Business Media. This book was released on 2008-02-04 with total page 237 pages. Available in PDF, EPUB and Kindle. Book excerpt: Leading researchers and innovators describe in step-by-step detail the latest techniques that promise to significantly impact the practice of proteomics, as well as its success in developing novel clinical agents. The methods span the entire spectrum of top-down and bottom-up approaches, including microarrays, gels, chromatography, and affinity separations, and address every aspect of the human proteome, both quantitatively and qualitatively. The techniques of protein detection utilized are diverse and range from fluorescence and resonance light scattering to surface plasmon resonance and mass spectrometry. The protocols follow the successful Methods in Molecular BiologyTM series format, each offering step-by-step laboratory instructions, an introduction outlining the principles behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.
Download or read book The Development and Application of Methods for Activity based Protein Profiling written by Nadim Jessani and published by . This book was released on 2004 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt: Considering that proteins mediate nearly all biochemical events underlying cell and organismal physiology and pathophysiology, the need to develop general methods to measure levels and activities of these biomolecules directly in cell, and tissue proteomes is apparent. The ability to profile classes of proteins based on activity would greatly accelerate assignment of protein function and identification of new biomarkers and therapeutic targets for the diagnosis and treatment of human disease. These issues have engendered a new breed of comparative proteomic strategies, in which the complex array of proteins expressed by a given biological sample are parceled into manageable fractions prior to analysis. Described here is a chemical proteomics method, "activity-based protein profiling" (ABPP), that was developed to compliment conventional genomic and proteomic methods that focus on measuring abundance rather than activity . ABPP employs chemical probes to covalently label active sites of enzyme superfamilies in a manner that provides a direct readout of changes in catalytic activity. By providing a covalent link between labeled proteins and a chemical tag, ABPP permits the consolidated detection, isolation, and identification of active enzymes directly from samples of high biological complexity. This work represents the application of ABPP for the functional analysis of human cancer. First, we demonstrate the utility of ABPP in classifying phenotypically distinct classes of human cancer lines based on enzyme activity profiles of their secreted and membrane proteomes. These studies are then extended to the profiling of primary human tumors as well as an established mouse model of human cancer, demonstrating the dramatic functional differences that exist between cancer cells grown in culture or in the context of in vivo tumor growth, both of which serve as important, widely used, research models of human cancer. Also shown, is the use of ABPP to assign novel constituents to otherwise well characterized enzyme families. Finally, the development and application of activity-based probes directed at the metalloprotease family of enzymes is described. Collectively, these studies establish ABPP as a powerful strategy for the functional analysis of large panels of cells/tissues, or to obtain in-depth information on a few samples, or even individual enzymes.
Download or read book Proteomics of Human Body Fluids written by Visith Thongboonkerd and published by Springer Science & Business Media. This book was released on 2008-01-23 with total page 536 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume is the first collection of applications of proteomics to analyze various human body fluids. Proteomics of Human Bodyfluids consists of two parts. The first provides basic principles and strategies for proteomic analysis of human body fluids. The second offers more details regarding methodologies and recent findings and clinical applications of each specific type of human body fluids.
Download or read book Frontiers in Natural Product Chemistry written by Atta-ur-Rahman and published by Bentham Science Publishers. This book was released on 2017-08-11 with total page 365 pages. Available in PDF, EPUB and Kindle. Book excerpt: Frontiers in Natural Product Chemistry is a book series devoted to publishing monographs that highlight important advances in natural product chemistry. The series covers all aspects of research in the chemistry and biochemistry of naturally occurring compounds including coverage of work on natural substances of land and sea and of plants, microbes and animals. Reviews of structure elucidation, biological activity, organic and experimental synthesis of natural products as well as developments of new methods are included. The third volume of the series brings seven reviews covering natural products from marine plant sources, natural oligosaccharides, topical sesquiterpenes for pain treatment, biological activity of piperidinols and much more.
Download or read book Target Discovery and Validation written by Alleyn T. Plowright and published by John Wiley & Sons. This book was released on 2020-02-18 with total page 396 pages. Available in PDF, EPUB and Kindle. Book excerpt: The modern drug developers? guide for making informed choices among the diverse target identification methods Target Discovery and Validation: Methods and Strategies for Drug Discovery offers a hands-on review of the modern technologies for drug target identification and validation. With contributions from noted industry and academic experts, the book addresses the most recent chemical, biological, and computational methods. Additionally, the book highlights techologies that are applicable to ?difficult? targets and drugs directed at multiple targets, including chemoproteomics, activity-based protein profiling, pathway mapping, genome-wide association studies, and array-based profiling. Throughout, the authors highlight a range of diverse approaches, and target validation studies reveal how these methods can support academic and drug discovery scientists in their target discovery and validation research. This resource: -Offers a guide to identifying and validating targets, a key enabling technology without which no new drug development is possible -Presents the information needed for choosing the appropriate assay method from the ever-growing range of available options -Provides practical examples from recent drug development projects, e. g. in kinase inhibitor profiling Written for medicinal chemists, pharmaceutical professionals, biochemists, biotechnology professionals, and pharmaceutical chemists, Target Discovery and Validation explores the current methods for the identification and validation of drug targets in one comrpehensive volume. It also includes numerous practical examples.
Download or read book Advanced Chemical Biology written by Howard C. Hang and published by John Wiley & Sons. This book was released on 2023-02-06 with total page 806 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advanced Chemical Biology The modern approach to teaching chemical biology Advanced Chemical Biology is organized around the central dogma of life, progressing from genes to proteins and higher-order cellular structures, including core application areas such as imaging, chemical genetics, activity-based protein profiling, and natural product discovery and biosynthesis. Advanced topics and applications in, e. g., microbiology, developmental biology, and neurobiology, are covered in separate sections. Every chapter is homogeneous in style and layout, consisting of a short historical introduction followed by a description of the underlying concepts and a selection of recent examples of how the concept has been turned into practice. The subdivision of the contents into core and supplemental chapters enables a flexible use in teaching, both for a one-semester and a two-semester course. Written by authors and editors coming from the leading scientific institutions that have developed the concepts and technologies for this discipline, Advanced Chemical Biology includes specific information on topics like: DNA function, synthesis and engineering, chemical approaches to genome integrity, and RNA function, synthesis, and probing Chemical approaches to transcription and RNA regulation in vivo, chemical biology of genome engineering, and peptide/protein synthesis and engineering Directed evolution for chemical biology, chemical biology of cellular metabolism, chemical biology of lipids, and protein post-translational modifications Chemical glycobiology, chemical and enzymatic modification of proteins, genetic code expansion, bio-orthogonal chemistry, and cellular imaging With its broad scope and focus on turning concepts into applications, Advanced Chemical Biology is an excellent starting point for anyone entering the field and looking for a guide to the wide range of available methods and strategies that chemical biology has to offer. With a Foreword by Nobel Laureate Carolyn Bertozzi.
