The handle http://hdl.handle.net/1887/29763 holds various files of this Leiden University dissertation
Author: Zweemer, Annelien
Title: The ins and outs of ligand binding to CCR2
Issue Date: 2014-11-20
The INS and OUTS of ligand binding to CCR2
Annelien Jacomina Maria Zweemer
Amsterdam (Amsterdam, The Netherlands).
This thesis was printed by Gildeprint (Enschede, The Netherlands).
The printing of this thesis was financially supported by PeproTech.
Cover design: Esmee Gramberg - www.annageemag.com
© Annelien Zweemer 2014. All rights reserved.
No part of this thesis may be reproduced in any form without the prior written permission of the holder of copyright.
The INS and OUTS of ligand binding to CCR2
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 20 november 2014
klokke 16:15 uur
door
Annelien Jacomina Maria Zweemer
geboren te Goes in 1985
Overige Leden: Prof. Dr. M.M. Rosenkilde Prof. Dr. B. van de Water Prof. Dr. J. Kuiper
Prof. Dr. P.H. van de Graaf
Contents
Chapter 1 General introduction 7
Chapter 2 Bias in chemokine receptor signalling 23
Chapter 3 Multiple binding sites for small molecule antagonists at the
chemokine receptor CCR2 45
Chapter 4 Discovery and mapping of an intracellular antagonist binding site
at the chemokine receptor CCR2 71
Chapter 5 Allosteric modulation of the chemokine receptor CCR2 by amiloride
analogues and sodium ions 97
Chapter 6 Structure-kinetics relationships – an overlooked parameter in hit-to- lead optimization: a case of cyclopentylamines as CCR2 antagonists 121
Chapter 7 Conclusions and future perspectives 143
Summary 159
Samenvatting 163
List of publications 169
Curriculum Vitae 173
Acknowledgements 177
