Optical Control of Dopamine D2-like Receptors with Cell-Specific Fast-Relaxing Photoswitches

Hetzler, Belinda E.; Donthamsetti, Prashant; Peitsinis, Zisis; Stanley, Cherise; Trauner, Dirk; Isacoff, Ehud Y.

doi:10.1021/jacs.3c02735

Title: Optical Control of Dopamine D2-like Receptors with Cell-Specific Fast-Relaxing Photoswitches

Journal Article · Wed Aug 16 00:00:00 UTC 2023 · Journal of the American Chemical Society

DOI: https://doi.org/10.1021/jacs.3c02735 · OSTI ID:2470610

^[1]; Donthamsetti, Prashant ^[2]; Peitsinis, Zisis ^[1]; Stanley, Cherise ^[2]; Trauner, Dirk ^[3];

^[4]

New York Univ. (NYU), NY (United States)
University of California, Berkeley, CA (United States)
New York Univ. (NYU), NY (United States); Univ. of Pennsylvania, Philadelphia, PA (United States)
University of California, Berkeley, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Dopamine D2-like receptors (D2R, D3R, and D4R) control diverse physiological and behavioral functions and are important targets for the treatment of a variety of neuropsychiatric disorders. Their complex distribution and activation kinetics in the brain make it difficult to target specific receptor populations with sufficient precision. We describe a new toolkit of light-activatable, fast-relaxing, covalently taggable chemical photoswitches that fully activate, partially activate, or block D2-like receptors. This technology combines the spatiotemporal precision of a photoswitchable ligand (P) with cell type and spatial specificity of a genetically encoded membrane anchoring protein (M) to which the P tethers. These tools set the stage for targeting endogenous D2-like receptor signaling with molecular, cellular, and spatiotemporal precision using only one wavelength of light.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2470610

Journal Information:: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 34 Vol. 145; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Title: Optical Control of Dopamine D2-like Receptors with Cell-Specific Fast-Relaxing Photoswitches

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