by Keyword: Muscarinic ligands
Gerwe, Hubert, Schaller, Eva, Sortino, Rosalba, Opar, Ekin, Martinez-Tambella, Joaquin, Bermudez, Marcel, Lane, J Robert, Gorostiza, Pau, Decker, Michael, (2024). Photo-BQCA: Positive Allosteric Modulators Enabling Optical Control of the M1 Receptor Angewandte Chemie (International Ed. Print) , e202411438
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-1 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-1 receptor signaling and a proof of concept for photoswitchable allosteric modulators at Class A receptors.
JTD Keywords: Agonist, Allosterism, Gpcr, Muscarinic ligands, Photopharmacology, Photoswitc, Selective activation, Serie
