Mass spectrometry of oligosaccharides

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I. Introduction 162 II. CHARACTERISTICS OF TANDEM MASS SPECTRA OF CARBOHYDRATES 163 A. Ionization of Carbohydrates 163 1. Electrospray Ionization (ESI) 163 2. Matrix‐Assisted Laser Desorption/Ionization (MALDI) 163 B. Nomenclature for the Fragmentation of Glycoconjugates 164 C. Tandem MS of Native Oligosaccharide Molecular Ions 165 1. Protonated Ions 165 2. Deprotonated Ions 166 3. Alkali and Alkaline Earth Adducted Ions 166 D. Tandem MS of Permethylated and Peracetylated Oligosaccharides 169 E. Tandem MS of Reductively Aminated Carbohydrates 170 F. Discrimination of Monosaccharide Linkages 171 G. Gas‐Phase Degradation of Oligosaccharides 178 H. Computer‐Based Approaches for Interpretation of Oligosaccharide Product‐Ion Mass Spectra 181 I. Internal Residue Loss Rearrangements of Oligosaccharide Ions During CID 183 J. Conclusions 184 III. ANALYZERS FOR MASS SPECTROMETRY OF CARBOHYDRATES 186 A. Analysis of Permethylated Carbohydrates Using High Temperature GC/MS 186 B. Analysis of Carbohydrates with MALDI‐TOF MS 186 C. Analysis of Carbohydrates with MALDI Q‐oTOF MS 187 D. Analysis of Carbohydrates with ESI Q‐oTOF MS 187 E. Analysis of Carbohydrates with QIT MS 187 F. Analysis of Glycoconjugates with FT MS 188 G. Conclusions 188 IV. TANDEM MASS SPECTROMETRY OF GLYCOPEPTIDES 189 A. Ionization of Glycopeptides 189 B. CID of Glycopeptides 190 1. Selective Identification of Glycopeptides with Tandem MS 190 2. CID of O‐Linked Glycopeptides 191 3. CID of N‐Linked Glycopeptides 191 C. Electron Capture Dissociation of Glycopeptides 193 D. Conclusions 193 V. MASS SPECTROMETRY OF SIALYLATED GLYCOCONJUGATES 195 A. Permethylation of Sialylated Oligosaccharides 195 B. MALDI‐MS of Sialylated Glycoconjugates 195 1. Anionic Dopants for Analysis of Sialylated Glycoconjugates 196 2. Methyl Esterification to Stabilize Sialic Acid Residues 196 3. Perbenzolylation to Stabilize Sialic Acid Residues 196 4. High‐Pressure MALDI of Sialylated Glycoconjugates 196 C. ESI MS of Sialylated Oligosaccharides 197 D. Tandem MS of Sialylated Oligosaccharides 198 E. Conclusions 199 VI. MASS SPECTROMETRY OF SULFATED OLIGOSACCHARIDES 199 A. Derivatization 199 B. Ionization Methods 199 1. Fast Atom Bombardment 199 2. MALDI 202 a. MALDI of Sulfated Peptides 202 b. Direct MALDI of Sulfated Oligosaccharides 202 c. Use of Basic Peptides for MALDI of Polysulfated Oligosaccharides 203 d. MALDI Analysis of Protein‐Sulfated Oligosaccharide Complexes 204 3. ESI of Sulfated Oligosaccharides 205 4. On‐Line Separation Systems for Sulfated Carbohydrates 206 C. Tandem MS of Sulfated Oligosaccharides 206 1. Lessons from CID of Sulfated Peptides 206 2. Tandem MS of Mono‐ and Di‐Sulfated Oligosaccharides 207 3. Precursor‐Ion and Neutral‐Loss Scans for Sulfated Glycoconjugates 208 4. Determination of Positional Sulfation Isomers in GAG Disaccharides 208 5. Tandem Mass Spectrometric Quantification of GAG Disaccharides 209 6. Tandem Mass Spectrometric Analysis of GAG Oligosaccharides 211 a. CS Oligosaccharides 211 b. Heparin/HS Oligosaccharides 214 D. Conclusions 214 VII. OVERALL CONCLUSIONS 215 VIII. ABBREVIATIONS 215 References 216 Glycosylation is a common post‐translational modification to cell surface and extracellular matrix (ECM) proteins as well as to lipids. As a result, cells carry a dense coat of carbohydrates on their surfaces that mediates a wide variety of cell–cell and cell–matrix interactions that are crucial to development and function. Because of the historical difficulties with the analysis of complex carbohydrate structures, a detailed understanding of their roles in biology has been slow to develop. Just as mass spectrometry has proven to be the core technology behind proteomics, it stands to play a similar role in the study of the functional implications of carbohydrate expression, known as glycomics. This review summarizes the state of knowledge for the mass spectrometric analysis of oligosaccharides with regard to neutral, sialylated, and sulfated compound classes. Mass spectrometric techniques for the ionization and fragmentation of oligosaccharides are discussed so as to give the reader the background to make informed decisions to solve structure‐activity relations in glycomics. © 2004 Wiley Periodicals, Inc., Mass Spec Rev 23:161–227, 2004.