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OverviewThe book that highlights mass spectrometry and its application in characterizing proteins and peptides in drug discovery An instrumental analytical method for quantifying the mass and characterization of various samples from small molecules to large proteins, mass spectrometry (MS) has become one of the most widely used techniques for studying proteins and peptides over the last decade. Bringing together the work of experts in academia and industry, Protein and Peptide Mass Spectrometry in Drug Discovery highlights current analytical approaches, industry practices, and modern strategies for the characterization of both peptides and proteins in drug discovery. Illustrating the critical role MS technology plays in characterizing target proteins and protein products, the methods used, ion mobility, and the use of microwave radiation to speed proteolysis, the book also covers important emerging applications for neuroproteomics and antigenic peptides. Placing an emphasis on the pharmaceutical industry, the book stresses practice and applications, presenting real-world examples covering the most recent advances in mass spectrometry, and providing an invaluable resource for pharmaceutical scientists in industry and academia, analytical and bioanalytical chemists, and researchers in protein science and proteomics. Full Product DetailsAuthor: Michael L. Gross , Guodong Chen , Birendra PramanikPublisher: John Wiley & Sons Inc Imprint: John Wiley & Sons Inc Dimensions: Width: 16.30cm , Height: 3.10cm , Length: 24.10cm Weight: 0.875kg ISBN: 9780470258170ISBN 10: 0470258179 Pages: 484 Publication Date: 23 December 2011 Audience: Professional and scholarly , Professional & Vocational Format: Hardback Publisher's Status: Active Availability: Out of stock  The supplier is temporarily out of stock of this item. It will be ordered for you on backorder and shipped when it becomes available. Table of ContentsPREFACE xv CONTRIBUTORS xvii PART I METHODOLOGY 1 1 Ionization Methods in Protein Mass Spectrometry 3 Ismael Cotte-Rodriguez, Yun Zhang, Zhixin Miao, and Hao Chen 1.1 History of the Development of Protein Mass Spectrometry 4 1.2 Laser-Based Ionization Methods for Proteins 5 1.3 Spray-Based Ionization Methods for Proteins 13 1.4 Ambient Ionization Methods 20 1.5 Conclusions 30 Acknowledgments 30 References 30 2 Ion Activation and Mass Analysis in Protein Mass Spectrometry 43 Cheng Lin and Peter O’Connor 2.1 Introduction 43 2.2 Ion Activation and Tandem MS Analysis 46 2.3 Mass Analyzers 59 References 81 3 Target Proteins: Bottom-up and Top-down Proteomics 89 Michael Boyne and Ron Bose 3.1 Mass Spectral Approaches to Targeted Protein Identification 89 3.2 Bottom-up Proteomics 90 3.3 Top-down Approaches 96 3.4 Next-Generation Approaches 98 References 99 4 Quantitative Proteomics by Mass Spectrometry 101 Jacob Galan, Anton Iliuk, and W. Andy Tao 4.1 Introduction 101 4.2 In-Cell Labeling 105 4.3 Quantitation via Isotopic Labeling of Proteins 107 4.4 Quantitation via Isotopic Labeling on Peptides 112 4.5 Label-Free Quantitation 116 4.6 Conclusions 119 Acknowledgment 120 References 120 5 Comparative Proteomics by Direct Tissue Analysis Using Imaging Mass Spectrometry 129 Michelle L. Reyzer and Richard M. Caprioli 5.1 Introduction 129 5.2 Conventional Comparative Proteomics 130 5.3 Comparative Proteomics Using Imaging MS 131 5.4 Conclusions 136 Acknowledgments 137 References 137 6 Peptide and Protein Analysis Using Ion Mobility–Mass Spectrometry 139 Jeffrey R. Enders, Michal Kliman, Sevugarajan Sundarapandian, and John A. McLean 6.1 Ion Mobility–Mass Spectrometry: Instrumentation and Separation Selectivity 139 6.2 Characterizing and Interpreting Peptide and Protein Structures 147 6.3 Applications of IM-MS to Peptide and Protein Characterizations 152 6.4 Future Directions 158 Acknowledgments 159 References 160 7 Chemical Footprinting for Determining Protein Properties and Interactions 175 Sandra A. Kerfoot and Michael L. Gross 7.1 Introduction to Hydrogen–Deuterium Exchange 175 7.2 Experimental Procedures 178 7.3 Mass Spectrometry-Based HDX in Practice 182 7.4 Protein Footprinting via Free-Radical Oxidation 193 7.5 Chemical Crosslinking 198 7.6 Selective and Irreversible Chemical Modification 201 7.7 Conclusion 205 References 206 8 Microwave Technology to Accelerate Protein Analysis 213 Urooj A. Mirza, Birendra N. Pramanik, and Ajay K. Bose 8.1 Introduction 213 8.2 Microwave Technology 215 8.3 Summary 224 Acknowledgments 224 References 224 9 Bioinformatics and Database Searching 231 Surendra Dasari and David L. Tabb 9.1 Overview 231 9.2 Introduction to Tandem Mass Spectrometry 231 9.3 Overview of Peptide Identification with Database Searching 234 9.4 MyriMatch-IDPicker Protein Identification Pipeline 235 9.5 Results of a Shotgun Proteomics Study 246 9.6 Improvements to MyriMatch Database Search Engine 248 9.7 Applications of MyriMatch-IDPicker Pipeline 250 9.8 Conclusions 251 Acknowledgments 251 References 251 PART II Applications 253 10 Mass Spectrometry-Based Screening and Characterization of Protein–Ligand Complexes in Drug Discovery 255 Christine L. Andrews, Michael R. Ziebell, Elliott Nickbarg, and Xianshu Yang 10.1 Introduction 255 10.2 Affinity Selection Mass Spectrometry (AS-MS) 256 10.3 Solution-Based AS-MS as Screening Technologies 258 10.4 Gas-Phase Interactions 267 10.5 Enzyme Activity Assays Using MS for Screening or Confirming Drug Candidates 271 10.6 Conclusions and Future Directions 276 References 277 11 Utilization of Mass Spectrometry for the Structural Characterization of Biopharmaceutical Protein Products 287 Amareth Lim and Catherine A. Srebalus Barnes 11.1 Introduction 287 11.2 MS-Based Approach for the Characterization of Recombinant Therapeutic Proteins 288 11.3 Cell Culture Development 290 11.4 Purification Development 294 11.5 Formulation Development 300 11.6 Analytical Method Development 304 11.7 Confirmation of Structure/Product Comparability Assessment 311 11.8 Conclusions 313 Acknowledgments 315 References 315 12 Post-translationally Modified Proteins: Glycosylation, Phosphorylation, and Disulfide Bond Formation 321 Anthony Tsarbopoulos and Fotini N. Bazoti 12.1 Introduction 321 12.2 Glycosylation 322 12.3 Phosphorylation 338 12.4 Disulfide Bond Detection and Mapping 347 12.5 Future Perspectives 350 Acknowledgments 352 Abbreviations 353 References 354 13 Mass Spectrometry of Antigenic Peptides 371 Henry Rohrs 13.1 Introduction 371 13.2 Analysis of Antigenic Peptides 374 13.3 Examples of the Application of Mass Spectrometry to Antigenic Peptide Study 381 13.4 Future Work 385 Acknowledgments 386 Abbreviations 387 References 387 14 Neuropeptidomics 393 Jonathan V. Sweedler, Fang Xie, and Adriana Bora 14.1 Introduction 393 14.2 Neuropeptidomics: Characterizing Peptides in the Brain 394 14.3 Sample Preparation for Mass Spectrometry 395 14.4 Separations 405 14.5 Peptide Characterization via Mass Spectrometry 407 14.6 Conclusions 419 14.7 Future Perspectives 419 Acknowledgments 420 References 420 15 Mass Spectrometry for the Study of Peptide Drug Metabolism 435 Patrick J. Rudewicz 15.1 Introduction 435 15.2 Peptide Drug Metabolism 436 15.3 LC-MS/MS for Metabolite Identification 437 15.4 Quantitative Analysis 439 15.5 Case Study: IL-1b Protease Inhibitors 440 15.6 Future Directions 445 References 445 INDEX 449Reviews<p> This book will be a valuable reference as it contains plenty ofdepth and substance to be of interest to experienced practitionersof mass spectrometry and related techniques, but is stillaccessible to pharmaceutical researchers who want to learn moreabout MS technologies and its applications. (AmericanSociety for Mass Spectrometry, 1 July 2012) <p> <p> This book will be a valuable reference as it contains plenty of depth and substance to be of interest to experienced practitioners of mass spectrometry and related techniques, but is still accessible to pharmaceutical researchers who want to learn more about MS technologies and its applications. (American Society for Mass Spectrometry, 1 July 2012) This book will be a valuable reference as it contains plenty of depth and substance to be of interest to experienced practitioners of mass spectrometry and related techniques, but is still accessible to pharmaceutical researchers who want to learn more about MS technologies and its applications. (American Society for Mass Spectrometry, 1 July 2012) Author InformationMichael L. Gross, PhD, is a Professor in the Departments of Chemistry, Medicine, and Immunology at Washington University in St. Louis. He is also Principal Investigator at the National Institutes of Health (NIH) Research Resource in Mass Spectrometry. Guodong Chen, PhD, is Principal Scientist in Bioanalytical and Discovery Analytical Sciences at Bristol-Myers Squibb in Princeton, New Jersey. He heads a mass spectrometry group in support of drug discovery as well as development programs in small molecule pharmaceuticals and biologics. Birendra N. Pramanik, PhD, was a Distinguished Fellow at Schering-Plough Research Institute (SPRI), where he directed the spectroscopy, mass spectrometry, and NMR programs. Tab Content 6Author Website:Countries AvailableAll regions |
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