Cover Page
The handle http://hdl.handle.net/1887/61076 holds various files of this Leiden University dissertation.
Author: Reiding, K.R.
Title: High-throughput mass spectrometric N-glycomics
Issue Date: 2018-04-05
High-throughput mass spectrometric N-glycomics
Karli Robert Reiding
ISBN: 978-94-6295-891-3
© Karli Reiding. All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means without permission of the author or the journals holding the copyrights of the published manuscripts. All published material was reprinted with permission.
The work presented in this thesis was performed at the Center for Proteomics and Metabolomics, Leiden University Medical Center, The Netherlands.
The work was supported by the European Union Seventh Framework Programme HighGlycan project, grant number: 278535.
Cover and chapter design: Boudien Reiding & Karli Reiding Printing: ProefschriftMaken || www.proefschriftmaken.nl
High-throughput mass spectrometric N-glycomics
Proefschrift ter verkrijging van
de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties te verdedigen op donderdag 5 april 2018
klokke 10.00 uur door Karli Robert Reiding geboren te Rotterdam
in 1985
Promotores: Prof.dr. M. Wuhrer Prof.dr. A.M. Deelder Leden promotiecommissie: Prof.dr. C.H. Hokke
Prof.dr. P.E. Slagboom
Dr. R. Fahey (NIBRT Glycoscience Group, National Institute for Bioprocessing Research and Training, Dublin, Ireland) Dr. D.J. Lefeber (Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands;
Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands)
Table of contents
Chapter 1 – General introduction ... 9
1.1 Glycosylation ... 11
1.2 Monosaccharide structure ... 12
1.3 The biosynthesis of protein N-glycosylation ... 14
1.4 Glycosylation in health and disease ... 16
1.5 Glycan analysis ... 18
1.6 Matrix-assisted laser desorption/ionization mass spectrometry ... 19
1.7 Chemical derivatization for MALDI-MS glycan analysis ... 21
1.8 Scope ... 23
1.9 References ... 24
Chapter 2 – High-throughput analysis and automation for glycomics studies ... 31
2.1 Abstract ... 32
2.2 Introduction ... 33
2.3 High-throughput sample preparation ... 35
2.4 Use of internal standards ... 40
2.5 Integration of analysis workflows ... 42
2.6 Automation of sample preparation... 43
2.7 Data analysis ... 45
2.8 Conclusion ... 46
2.9 Acknowledgments ... 49
2.10 References ... 49
Chapter 3 – High-throughput profiling of protein N-glycosylation by MALDI-TOF-MS
employing linkage-specific sialic acid esterification ... 55
3.1 Abstract ... 56
3.2 Introduction ... 57
3.3 Experimental section ... 58
3.4 Results ... 63
3.5 Discussion ... 71
3.6 Supporting information ... 72
3.7 Acknowledgments ... 73
3.8 References ... 73
Chapter 4 – Automation of high-throughput mass spectrometry-based plasma N-glycome analysis with linkage-specific sialic acid esterification ... 77
4.1 Abstract ... 78
4.2 Introduction ... 79
4.3 Experimental section ... 80
4.4 Results and discussion ... 84
4.5 Conclusion ... 87
4.6 Supporting information ... 87
4.7 Acknowledgments ... 88
4.8 References ... 88
Chapter 5 – Murine plasma N-glycosylation traits associated with sex and strain ... 91
5.1 Abstract ... 92
5.2 Introduction ... 93
5.3 Experimental section ... 94
5.4 Results ... 97
5.5 Discussion ... 103
5.6 Conclusions and perspectives ... 106
5.7 Acknowledgments ... 107
5.8 References ... 107
Chapter 6 – Human plasma N-glycosylation as analyzed by MALDI-FTICR-MS associates
with markers of inflammation and metabolic health ... 111
6.1 Abstract ... 112
6.2 Introduction ... 113
6.3 Experimental procedures ... 114
6.4 Results ... 119
6.5 Discussion ... 128
6.6 Supporting information ... 132
6.7 Acknowledgments ... 132
6.8 References ... 132
Chapter 7 – Serum protein N-glycosylation changes with rheumatoid arthritis disease activity during and after pregnancy ... 139
7.1 Abstract ... 140
7.2 Introduction ... 141
7.3 Methods ... 142
7.4 Results ... 144
7.5 Discussion ... 149
7.6 Summary ... 151
7.7 Acknowledgments ... 151
7.8 Additional information ... 151
7.9 References ... 151
Chapter 8 – High-throughput serum N-glycomics: method comparison and application to study rheumatoid arthritis and pregnancy-associated changes ... 155
8.1 Abstract ... 156
8.2 Introduction ... 157
8.3 Results ... 158
8.4 Discussion ... 166
8.5 Summary ... 169
8.6 Methods ... 170
8.7 References ... 172
Chapter 9 – General discussion ... 177
9.1 Developments in linkage-specific sialic acid esterification ... 179
9.2 Persistent challenges in mass spectrometric N-glycomics ... 181
9.3 Developments human plasma N-glycosylation analysis ... 185
9.4 Future prospects of plasma N-glycosylation analysis by MALDI-MS ... 190
9.5 Concluding remarks ... 192
9.6 References ... 193
English summary ... 203
Nederlandse samenvatting ... 207
Acknowledgements ... 211
Curriculum Vitae ... 212
Publications and submitted manuscripts ... 213
