A Photoswitchable Dualsteric Ligand Controlling Receptor Efficacy

Angewandte Chemie
Luca AgnettaMichael Decker

Abstract

The 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.

References

May 3, 2003·Pharmacology & Therapeutics·Chris J van Koppen, Björn Kaiser
Sep 23, 2003·Journal of Molecular Neuroscience : MN·Abraham FisherRachel Brandeis
Dec 16, 2003·Proceedings of the National Academy of Sciences of the United States of America·Moritz BünemannMartin J Lohse
Jul 3, 2004·The Journal of Biological Chemistry·Viacheslav O NikolaevMartin J Lohse
Aug 2, 2006·Autonomic & Autacoid Pharmacology·R M Eglen
Sep 1, 2007·Nature Reviews. Drug Discovery·Jürgen WessDinesh Gautam
May 31, 2011·BMC Biology·Merel J W Adjobo-HermansTheodorus W J Gadella
Nov 28, 2012·Trends in Pharmacological Sciences·J Robert LaneArthur Christopoulos
Nov 12, 2013·Nature Chemical Biology·Andreas BockKlaus Mohr
Jan 25, 2014·Journal of the American Chemical Society·Willem A VelemaBen L Feringa
Jul 10, 2014·The Journal of Biological Chemistry·Peter KeovArthur Christopoulos
Dec 6, 2014·Journal of Medicinal Chemistry·Xinyu ChenMichael Decker
Jun 24, 2015·Accounts of Chemical Research·Johannes BroichhagenDirk Trauner
Aug 16, 2015·British Journal of Pharmacology·R SchrageK Mohr
Nov 13, 2015·British Journal of Pharmacology·A D Stumpf, C Hoffmann
Mar 10, 2016·Nature·David M ThalArthur Christopoulos
Jun 15, 2016·The Journal of Biological Chemistry·Andreas BockKlaus Mohr
Jul 5, 2016·Angewandte Chemie·Michael M LerchBen L Feringa

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Citations

Jan 26, 2018·Chemical Communications : Chem Comm·A Babalhavaeji, G A Woolley
Feb 23, 2020·Beilstein Journal of Organic Chemistry·Alexander SailerOliver Thorn-Seshold
Feb 23, 2020·Biomolecules·Jan Jakubik, Esam E El-Fakahany
Dec 14, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniela Volpato, Ulrike Holzgrabe
Jun 24, 2021·Journal of Medicinal Chemistry·Fabio RiefoloPau Gorostiza
Nov 23, 2017·Journal of the American Chemical Society·Prashant C DonthamsettiDirk Trauner
Apr 24, 2019·Journal of the American Chemical Society·Fabio RiefoloPau Gorostiza
Jul 10, 2018·Chemical Reviews·Katharina HüllDirk Trauner
Mar 11, 2020·Journal of Medicinal Chemistry·Yu-Hui JinZheng-Yu Jiang
Oct 20, 2020·ACS Pharmacology & Translational Science·Maria Ricart-OrtegaAmadeu Llebaria
Jul 21, 2020·Journal of Medicinal Chemistry·Anna Duran-CorberaXavier Rovira
Sep 19, 2019·ACS Medicinal Chemistry Letters·Micael R CunhaJean-Louis Reymond
Oct 23, 2018·Journal of the American Chemical Society·Carlo MateraPau Gorostiza

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