Cover Page The handle http://hdl.handle.net/26833 holds

Cover Page
The handle http://hdl.handle.net/1887/26833 holds various files of this Leiden University
dissertation.
Author: Guo, Dong
Title: Drug-target residence time : a case for the adenosine A1 and A2A receptors
Issue Date: 2014-06-25
Drug-target residence time
A c a s e f o r t h e a d e n o s i n e A 1 a n d A 2A r e c e p t o r s
Cover description: a putative trajectory of ZM241385 binding to or unbinding from
the human adenosine A2A receptor. The figure is generated with ICM browser v3.7
(Molsoft) based on the first adenosine A2A receptor crystal structure (PDB: 3EML).
Cover design: Dong Guo
Thesis layout: Dong Guo
Printed in the Netherlands
© Copyright, Dong Guo, 2014
All rights reserved. No part of this book may be reproduced in any form or by any
means without permission of the author.
ISBN: 978-94-61086-97-6
Drug-target residence time
A case for the adenosine A1 and A2A receptors
PROEFSCHRIFT
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van Rector Magnificus prof. dr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties
te verdedigen op woensdag 25 juni 2014
klokke 16.15 uur
door
Dong Guo
geboren te Xuzhou, P. R. China
in 1984
Promotiecommissie
Promotor:
Prof. Dr. A. P. IJzerman
Copromotor:
Dr. L. H. Heitman
Overige leden:
Prof. Dr. P. H. van der Graaf
Prof. Dr. B. van de Water
Prof. Dr. M. Danhof
Prof. Dr. G. Vauquelin (Vrije Universiteit Brussel, Belgium)
to my parents
Contents
Chapter 1
General introduction
9
Chapter 2
Drug-target residence time: A case for G protein-coupled
receptors
25
Chapter 3
Dual-point competition association assay: A fast and
high-throughput kinetic screening method for assessing
ligand-receptor binding kinetics
81
Chapter 4
Binding kinetics of ZM241385 derivatives at the human
adenosine A2A receptor
109
Chapter 5
Functional efficacy of adenosine A2A receptor agonists is
positively correlated to their receptor residence time
145
Chapter 6
Molecular basis of allosteric modulation: Insight from
a binding kinetics study at the human adenosine A1
receptor
175
Chapter 7
Conclusions and perspectives
205
Summary
221
Samenvatting
223
Curriculum Vitae
227
List of publications
229
Acknowledgements
231

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