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Cover Page

The handle

http://hdl.handle.net/1887/87273

holds various files of this Leiden University

dissertation.

Author: Lahav, D.

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Fluorescence Polarization Activity-Based Protein

Profiling on Retaining Glycosidases

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 het besluit van het College voor Promoties te verdedigen op woensdag 8 april 2020

klokke 16.15 uur

door

Daniël Lahav

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Promotiecommissie

Promotor: Prof. dr. H. S. Overkleeft Copromotor: Prof. dr. J. M. F. G. Aerts

Promotiecommissie: Prof. dr. G. A. van der Marel Prof. dr. M. van der Stelt Overige commissieleden: Dr. J. D. C. Codée

Prof. dr. S. Py

Dr. G. Schulzenbacher Prof. dr. J. Brouwer Prof. dr. H. Ovaa

ISBN: 978-94-028-1979-3 Printed by: Ipskamp Printing

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Table of contents

Chapter 1 7

General Introduction

Chapter 2 17

A Fluorescence Polarization Activity-Based Protein Profiling

Assay in the Discovery of Potent, Selective Inhibitors for

Human Non-Lysosomal Glucosylceramidase

Chapter 3 49

FluoPol ABPP on Human Lysosomal β-Glucosylceramidase

Identifies Inhibitors from the LOPAC Library

Chapter 4 73

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Chapter 5 95

Competitive Fluorescence Polarization Activity Based Protein

Profiling allows the Discovery of New Golgi α-Mannosidase

Inhibitors

Chapter 6 117

Summary and Future Prospects

Samenvatting 123

List of Publications 125

Curriculum Vitae 126

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