Photo-BQCA: Positive Allosteric Modulators Enabling Optical Control of the M1 Receptor.
Angew Chem Int Ed Engl
; : e202411438, 2024 Aug 13.
Article
em En
| MEDLINE
| ID: mdl-39136071
ABSTRACT
The field of G protein-coupled receptor (GPCR) research has greatly benefited from the spatiotemporal resolution provided by light controllable, photoswitchable agents. 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 M1 muscarinic acetylcholine receptor. The presented benzyl quinolone carboxylic acid (BQCA) derivatives, photo-BQCisA and photo-BQCtrAns, exhibit complementary photopharmacological behavior and allow reversible control over the receptor using light as an external stimulus. This makes them valuable tools to further investigate M1 receptor signaling and a proof of concept for photoswitchable allosteric modulators at Class A receptors.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article