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Media type:
E-Article
Title:
A Photoswitchable Dualsteric Ligand Controlling Receptor Efficacy
Contributor:
Agnetta, Luca;
Kauk, Michael;
Canizal, Maria Consuelo Alonso;
Messerer, Regina;
Holzgrabe, Ulrike;
Hoffmann, Carsten;
Decker, Michael
Published:
Wiley, 2017
Published in:
Angewandte Chemie International Edition, 56 (2017) 25, Seite 7282-7287
Language:
English
DOI:
10.1002/anie.201701524
ISSN:
1521-3773;
1433-7851
Origination:
Footnote:
Description:
AbstractThe investigation of the mode and time course of the activation of G‐protein‐coupled receptors (GPCRs), in particular muscarinic acetylcholine (mACh or M) receptors, is still in its infancy despite the tremendous therapeutic relevance of M receptors and GPCRs in general. We herein made use of a dualsteric ligand that can concomitantly interact with the orthosteric, that is, the neurotransmitter, binding site and an allosteric one. We synthetically incorporated a photoswitchable (photochromic) azobenzene moiety. We characterized the photophysical properties of this ligand called BQCAAI and investigated its applicability as a pharmacological tool compound with a set of FRET techniques at the M1 receptor. BQCAAI proved to be an unprecedented molecular tool; it is the first photoswitchable dualsteric ligand, and its activity can be regulated by light. We also applied BQCCAI to investigate the time course of several receptor activation processes.