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Article Dans Une Revue ACS Chemical Neuroscience Année : 2024

Optical Control of Adenosine A 2A Receptor Using Istradefylline Photosensitivity

Résumé

In recent years, there has been growing interest in the potential therapeutic use of inhibitors of adenosine A2A receptors (A2AR) for the treatment of neurodegenerative diseases and cancer. Nevertheless, the widespread expression of A2AR throughout the body emphasizes the importance of temporally and spatially selective ligands. Photopharmacology is an emerging strategy that utilises photosensitive ligands to attain high spatiotemporal precision and regulate the function of biomolecules using light. In this study, we combined photochemistry, cellular and in vivo photopharmacology to investigate the light sensitivity of the FDA-approved antagonist istradefylline and its potential use as an A2AR photopharmacological tool. Our findings reveal that istradefylline exhibits rapid trans to cis isomerization under near UV light, and prolonged exposure results in the formation of photocycloaddition products. We demonstrate that exposure to UV light triggers a time-dependent decrease in the antagonistic activity of istradefylline in A2AR-expressing cells and enables real-time optical control of A2AR signaling in living cells and zebrafish. Together, these data demonstrate that istradefylline is a photoinactivatable A2AR antagonist and that this property can be utilized to perform photopharmacological experiments in living cells and animals.

Domaines

Pharmacologie
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Dates et versions

hal-04425630 , version 1 (30-01-2024)

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Anaëlle Dumazer, Xavier Gómez-Santacana, Fanny Malhaire, Chris Jopling, Damien Maurel, et al.. Optical Control of Adenosine A 2A Receptor Using Istradefylline Photosensitivity. ACS Chemical Neuroscience, inPress, 15 (3), pp.645-655. ⟨10.1021/acschemneuro.3c00721⟩. ⟨hal-04425630⟩
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