Analysis of Protein Post-Translational Modifications by Mass Spectrometry

Preface Post-translational Modification of Proteins Global versus Targeted Analysis Strategies Mass Spectrometric Analysis Methods for the Detection of PTMs Data-Dependent and Data-Independent Analyses Targeted Analyses Multiple Reaction Monitoring Multiple Reaction Monitoring Initiated Detection and Sequencing The Importance of Bioinformatics References Identification and Analysis of Protein Phosphorylation by Mass Spectrometry Introduction to Protein Phosphorylation Analysis of Protein Phosphorylation by Mass Spectrometry Global Analysis of Protein Phosphorylation by Mass Spectrometry Sample Preparation and Enrichment Strategies for Phosphoprotein Analysis by Mass Spectrometry Multidimensional Separations for Deep Coverage of the Phosphoproteome Computational and Bioinformatics Tools for Phosphoproteomics Concluding Remarks References Analysis of Protein Glycosylation by Mass Spectrometry Introduction General Structures of Carbohydrates Protein-Linked Glycans Isolation and Purification of Glycoproteins Lectin Affinity Chromatography Boronate-Based Compounds Hydrazide Enrichment Titanium Dioxide Enrichment of Sialylated Glycoproteins Mass Spectrometry of Intact Glycoproteins Site Analysis Glycan Release Use of Hydrazine Use of Reductive-Elimination Use of Enzymes Analysis of Released Glycans Cleanup of Glycan Samples Derivatization Derivatization at the Reducing Terminus Derivatization of Hydroxyl Groups: Permethylation Linkage Analysis Derivatization of Sialic Acids Exoglycosidase Digestions HPLC and ESI Mass Spectrometry of Glycans Aspects of Ionization for Mass Spectrometry Specific to the Analysis of Glycans Electron Impact (EI)Fast Atom Bombardment (FAB)Matrix-Assisted Laser Desorption/Ionization (MALDI)Electrospray Ionization (ESI)Glycan Composition by Mass Spectrometry Fragmentation Nomenclature of Fragment Ions In-Source Decay (ISD) Ions Postsource Decay (PSD) Ions Collision-Induced Dissociation (CID)Electron Transfer Dissociation (ETD)Infrared Multiphoton Dissociation (IRMPD)MSn Fragmentation Modes of Different Ion Types [M+H]+ Ions [M+Metal]+ Ions [M-H]- and [M+Anion]- Ions Ion Mobility Quantitative Measurements Computer Interpretation of MS Data Total Glycomics Methods Conclusions Abbreviations References Protein Acetylation and Methylation Overview of Protein Acetylation and Methylation Protein Acetylation Protein Methylation Functional Aspects Mass Spectrometry Analysis Mass Spectrometry Behavior of Modified Peptides MS Fragmentation Modes Acetylation- and Methylation-Specific Diagnostic Ions in MS Analysis Application of MS Methodologies for the Analysis of PTM Status Quantification Strategies Single Reaction Monitoring/Multiple Reaction Monitoring Parallel Reaction Monitoring Data-Independent Acquisition MS Ion Mobility MS Use of Stable Isotope-Labeled Precursors Dynamics of Acetylation and Methylation Stoichiometry of Acetylation and Methylation Global Analysis Top-Down Proteomics Middle Down Enrichment Immunoaffinity Enrichment Reader Domain-Based Capture Kac-Specific Capture Reagents Methyl-Specific Capture Reagents Biotin Switch-Based Capture Enrichment of N-Terminally Acetylated Peptides Bioinformatics Assigning Acetylation and Methylation Status PTM Repositories and Data Mining Tools Computational Prediction Tools for Acetylation and Methylation Sites Information for Design of Follow-Up Experiments Summary References Tyrosine Nitration Overview of Tyrosine Nitration MS Behavior of Nitrated Peptides Global Analysis of Tyrosine Nitration Enrichment Strategies Concluding Remarks Acknowledgements Abbreviations References Mass Spectrometry Methods for the Analysis of Isopeptides Generated from Mammalian Protein Ubiquitination and SUMOylation Overview of Ub and SUMO Biological Overview of Ubiquitin-Like Proteins Biological Overview of Ub and SUMO Biological Functions of Ub and SUMO Mass Spectrometry Behavior of Isopeptides Terminology of a Ub/Ubl isopeptide Mass Spectrometry Analysis of SUMO-Isopeptides Derived from Proteolytic Digestion Analysis of SUMO-Isopeptides with Typical Full-Length Tryptic Iso-chains Analysis of SUMO-Isopeptides with Atypical Tryptic Iso-chains and Shorter Iso-chains Derived from Alternative Digestion Strategies SUMO-Isopeptides with Atypical Iso-chains Generated from Tryptic Digestion Dual Proteolytic Enzyme Digestion with Trypsin and Chymotrypsin Proteolytic Enzyme and Chemical Digestion with Trypsin and Acid MS Analysis of Modified Ub- and SUMO-Isopeptides under CID Conditions SPITC Modification Dimethyl Modification m-TRAQ Modification Enrichment and Global Analysis of Isopeptides Overview of Enrichment Approaches K-GG Antibody SUMOylation Enrichment Concluding Remarks and Recommendations References The Deimination of Arginine to Citrulline Overview of Arginine to Citrulline Conversion: Biological Importance Mass Spectrometry-Based Proteomics Liquid Chromatography and Mass Spectrometry Behavior of Citrullinated Peptides Global Analysis of Citrullination Enrichment Strategies Bioinformatics Concluding Remarks References Glycation of Proteins Overview of Protein Glycation Mass Spectrometry Behavior of Glycated Peptides Global Analysis of Glycation Enrichment Strategies Bioinformatics Concluding Remarks References Biological Significance and Analysis of Tyrosine Sulfation Overview of Protein Sulfation Mass Spectrometry Behavior of Sulfated Peptides Enrichment Strategies and Global Analysis of Sulfation Sulfation Site Predictions Summary References The Application of Mass Spectrometry for the Characterization of Monoclonal Antibody-Based Therapeutics Introduction Antibody Structure N-Linked Glycosylation Antibody-Drug Conjugates Biosimilars Mass Spectrometry Solutions to Characterizing Monoclonal Antibodies Hyphenated Mass Spectrometry (X-MS) Techniques to Study Glycosylation Profiles Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS) to Characterize Monoclonal Antibody Structure Native Mass Spectrometry and the Use of IM-MS to Probe Monoclonal Antibody Structure Advanced Applications Quantifying Glycosylation Antibody-Drug Conjugates Biosimilar Characterization Concluding Remarks References