Photo‐BQCA: Positive Allosteric Modulators Enabling Optical Control of the M<sub>1</sub> Receptor
The field of G protein-coupled receptor (GPCR) research has greatly benefited from the spatiotemporal resolution provided by light controllable, i.e., photoswitchable ligands. Most of the developed tools have targeted the Rhodopsin-like family (Class A), the largest family of GPCRs. However, to date, all such Class A photoswitchable ligands were designed to act at the orthosteric binding site of these receptors. Herein, we report the development of the first photoswitchable allosteric modulators of Class A GPCRs, designed to target the M<sub>1</sub> muscarinic acetylcholine receptor. The presented benzyl quinolone carboxylic acid (BQCA) derivatives, Photo-BQCisA and Photo-BQCtrAns, exhibit complementary photopharmacological behavior and allow reversible control of the receptor using light as an external stimulus. This makes them valuable tools to further investigate M<sub>1</sub> receptor signaling and a proof of concept for photoswitchable allosteric modulators at Class A receptors.
Authors
- Ekin Opar (ORCID: https://orcid.org/0000-0002-1247-281X)
- Hubert Gerwe (ORCID: https://orcid.org/0000-0002-0642-3181)
- Michael Decker (ORCID: https://orcid.org/0000-0002-6773-6245)
- Marcel Bermúdez (ORCID: https://orcid.org/0000-0002-7421-3282)
- J. Robert Lane (ORCID: https://orcid.org/0000-0002-7361-7875)
- Rosalba Sortino (ORCID: https://orcid.org/0000-0002-8854-6782)
- Pau Gorostiza (ORCID: https://orcid.org/0000-0002-7268-5577)
- Joaquín Martínez‐Tambella (ORCID: https://orcid.org/0000-0001-7459-6749)
- E. Schaller
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- University of Nottingham (GB)
- University of Münster (DE)
- University of Würzburg (DE)
- Instituto de Salud Carlos III (ES)
- Centro de Investigación Biomédica en Red (ES)
- Queen's Medical Centre (GB)
- Institute for Bioengineering of Catalonia (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Angewandte Chemie International Edition
- Published
- 2024-08-13
- DOI
- https://doi.org/10.1002/anie.202411438
- Citations
- 3
- Primary Topic
- Photochromic and Fluorescence Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.35
Funders
- Centres de Recerca de Catalunya
- Deutsche Forschungsgemeinschaft
- Generalitat de Catalunya
- Studienstiftung des Deutschen Volkes
- Ministerio de Ciencia e Innovación
- Horizon 2020 Framework Programme
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Elitenetzwerk Bayern
- Agencia Estatal de Investigación
- FP7 Information and Communication Technologies
- HORIZON EUROPE European Innovation Council