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cc-by (c) Gerwe, Hubert et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/217335

Photo-BQCA: Positive Allosteric Modulators Enabling Optical Control of the M1 Receptor

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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.

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GERWE, Hubert, SCHALLER, Eva, SORTINO, Rosalba, OPAR, Ekin, MARTINEZ TAMBELLA, Joaquin, BERMUDEZ, Marcel, LANE, J robert, GOROSTIZA LANGA, Pablo ignacio, DECKER, Michael. Photo-BQCA: Positive Allosteric Modulators Enabling Optical Control of the M1 Receptor. _Angewandte Chemie-International Edition_. 2024. Vol. 63, núm. 47. [consulta: 20 de gener de 2026]. ISSN: 1433-7851. [Disponible a: https://hdl.handle.net/2445/217335]

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