Cover Page
The handle http://hdl.handle.net/1887/47526 holds various files of this Leiden University dissertation.
Author: Nederpelt, I.
Title: Time is of the essence - investigating kinetic interactions between drug, endogenous neuropeptides and receptor
Issue Date: 2017-04-06
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Time is of the essence
Investigating kinetic interactions between drug,
endogenous neuropeptides and receptor
2 Cover design: Rochelle Vergroesen & Indira Nederpelt
Cover art: Rochelle Vergroesen Thesis lay-out: Indira Nederpelt
Printing: GVO drukkers & vormgevers B.V., Ede
© Copyright, Indira Nederpelt, 2017 ISBN: 978-94-6332-161-7
All rights reserved. No part of this book may be reproduced in any form or by any means without permission of the author.
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Time is of the essence
Investigating kinetic interactions between drug, endogenous neuropeptides and receptor
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 donderdag 6 April 2017 klokke 16:15 uur
Door Indira Nederpelt
Geboren te Rotterdam, Nederland In 1988
4 Promotor: Prof. Dr. A.P. IJzerman
Co-promotor: Dr. L.H. Heitman
Promotie commissie:
Prof. Dr. H. Irth (chair)
Prof. Dr. J.A. Bouwstra (secretary)
Dr. E.C. de Lange (assistant professor of pharmacology at the LACDR, Leiden University)
Prof. Dr. G. Vauquelin (professor of molecular pharmacology at the Vrije Universiteit Brussel)
Prof. Dr. R.A. Adan (professor of molecular pharmacology at the Utrecht Medical Centre)
The research described in this thesis was performed at the department of Medicinal Chemistry of the Leiden Academic Centre for Drug Research (LACDR), Leiden University (Leiden, The Netherlands). The research was financially supported by EU/EFPIA Innovative Medicines Initiative Joint Undertaking, K4DD grant n° 115366.
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to my mother
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Index
Chapter 1 General Introduction 9-24
Chapter 2 Kinetic profile of neuropeptide – receptor interactions 25-42
Chapter 3 Characterization of 12 GnRH peptide agonists – a kinetic perspective
43-70
Chapter 4 Persistent GnRH receptor activation in pituitary αT3-1 cells analyzed with a label-free technology
71-88
Chapter 5 Kinetic binding and activation profiles of endogenous tachykinins targeting the NK1 receptor
89-107
Chapter 6 From receptor binding kinetics to signal transduction; a missing link in predicting in vivo drug-action
108-127
Chapter 7 Conclusions and future perspectives 128-142
Summary 143-148
Samenvatting 149-154
List of publications 155-158
Curriculum Vitae 159-162
Acknowledgements 163-165
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