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Glycomics based biomarkers of the rate of aging : development and applications of high-throughput N-glycan analysis

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Glycomics based biomarkers of the rate of aging :

development and applications of high-throughput N-glycan analysis

Ruhaak, L.R.

Citation

Ruhaak, L. R. (2011, March 24). Glycomics based biomarkers of the rate of aging : development and applications of high-throughput N-glycan analysis.

Retrieved from https://hdl.handle.net/1887/16559

Version: Corrected Publisher’s Version License:

Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/16559

Note: To cite this publication please use the final published version (if applicable).

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Glycomics based biomarkers of the rate of aging

Development and applications of high throughput N-glycan analysis

Lucia Renee Ruhaak

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GLYCOMICS BASED BIOMARKERS OF THE RATE OF AGING, BY L. RENEE RUHAAK. THESIS UNIVERSITY LEIDEN

©COPYRIGHT – L.R. RUHAAK, LEIDEN 2011. THE COPYRIGHT OF THE

ARTICLES THAT HAVE BEEN PUBLISHED OR ACCEPTED FOR PUBLICATION, HAVE BEEN TRANSFERRED TO THE RESPECTIVE JOURNALS AND / OR ORGANIZATIONS

LAY OUT: DHR. H. LOOTS

PRINTED BY: OFF PAGE, AMSTERDAM

COVER IMAGE: IMAGE COURTESY OF MUSEUM TWENTSEWELLE ENSCHEDE THE NETHER- LANDS (WWW.TWENTSEWELLE.NL). IMAGE WAS USED FOR THE POSTER OF THE EXHIBITION

“BETER DAN GOD” AT THIS MUSEUM.

ISBN XXX-XX-XXXXXXX-X

THE WORK DESCRIBED IN THIS THESIS WAS FUNDED BY AN INNOVATIVE ORIENTED RE- SEARCH (IOP) GRANT FROM THE DUTCH MINISTRY OF ECONOMIC AFFAIRS (GRANT NUMBER IGE-05007)

PRINTING OF THIS THESIS WAS FINANCIALLY SUPPORTED BY : J.E. JURRIAANSE STICHTING

DIONEX BENELUX B.V.

LUDGER LTD., UK

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Glycomics based biomarkers of the rate of aging

Development and applications of high throughput N-glycan analysis

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden,

op gezag van Rector Magnificus Prof. Mr. P.F. van der Heijden, volgens besluit van het College voor Promoties

te verdedigen op donderdag 24 maart 2011 klokke 15.00 uur

door

Lucia Renee Ruhaak geboren te Leiden in 1982

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Promotiecommissie

Promotores: Prof. Dr. A.M. Deelder Prof. Dr. P.E. Slagboom Co-promotor: Dr. M. Wuhrer

Overige leden: Prof. Dr. C.B. Lebrilla (University of California Davis, Department of Chemistry)

Prof. Dr. P.M. Rudd (University of Dublin, National Institute for Bioprocessing Research and Training)

Prof. Dr. R.G.J. Westendorp Prof. Dr. G.J. Mulder Prof. Dr. C. van Kooten Dr. C.H. Hokke

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Table of Contents

CHAPTER 1 INTRODUCTION 7

CHAPTER 2 A HILIC-BASED HIGH-THROUGHPUT SAMPLE PREPARATION METHOD FOR N-GLYCAN ANALYSIS FROM TOTAL HUMAN PLASMA

GLYCOPROTEINS 39

CHAPTER 3 2-PICOLINE-BORANE: A NON-TOXIC REDUCING

AGENT FOR OLIGOSACCHARIDE LABELING BY REDUCTIVE AMINATION 63

CHAPTER 4 OPTIMIZED WORKFLOW FOR PREPARATION OF

APTS-LABELED N-GLYCANS ALLOWING HIGH-THROUGHPUT ANALYSIS OF HUMAN PLASMA GLYCOMES USING 48-CHANNEL MULTIPLEXED

CGE-LIF 77

CHAPTER 5 PLASMA PROTEIN N-GLYCAN PROFILES ARE ASSOCIATED WITH CALENDAR AGE, FAMILIAL LONGEVITY AND HEALTH 105

CHAPTER 6 DECREASED LEVELS OF BISECTING GLCNAC

GLYCOFORMS OF IGG MARK HUMAN LONGEVITY 125

CHAPTER 7 HIGH-THROUGHPUT IMMUNO-AFFINITY CAPTURING

PROCEDURE FOR TARGETED GLYCAN-BASED BIOMARKER DISCOVERY:

APPLICATION TO AAT AND IGA 143

CHAPTER 8 GENERAL DISCUSSION 165

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