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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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Angewandte Chemie-International Edition, 2024, vol. 63, num. 47

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Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

# metadata.dc.title[].value
Photo-BQCA: Positive Allosteric Modulators Enabling Optical Control of the M1 Receptor