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

被引：7

作者：

Hetzler, Belinda E. ^{[1
]}

Donthamsetti, Prashant ^{[2
,3
]}

Peitsinis, Zisis ^{[1
]}

Stanley, Cherise ^{[2
]}

Trauner, Dirk ^{[1
,4
,5
]}

Isacoff, Ehud Y. ^{[2
,6
,7
,8
]}

机构：

[1] NYU, Dept Chem, New York, NY 10003 USA

[2] Univ Calif Berkeley, Mol & Cell Biol, Berkeley, CA 94720 USA

[3] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37235 USA

[4] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA

[5] Univ Penn, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA

[6] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA

[7] Univ Calif Berkeley, Weill Neurohub, Berkeley, CA 94720 USA

[8] Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2023年 / 145卷 / 34期

基金：

欧洲研究理事会; 美国国家卫生研究院;

关键词：

LIGANDS; D2; PHARMACOLOGY; AZOBENZENE; PHYSIOLOGY; DISCOVERY; MODULATE; AGONISTS; TOOLS; D-2L;

D O I：

10.1021/jacs.3c02735

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Dopamine D2-likereceptors (D2R, D3R, and D4R) control diversephysiological and behavioral functions and are important targets forthe treatment of a variety of neuropsychiatric disorders. Their complexdistribution and activation kinetics in the brain make it difficultto target specific receptor populations with sufficient precision.We describe a new toolkit of light-activatable, fast-relaxing, covalentlytaggable chemical photoswitches that fully activate, partially activate,or block D2-like receptors. This technology combines the spatiotemporalprecision of a photoswitchable ligand (P) with cell type and spatialspecificity of a genetically encoded membrane anchoring protein (M)to which the P tethers. These tools set the stage for targeting endogenousD2-like receptor signaling with molecular, cellular, and spatiotemporalprecision using only one wavelength of light.

引用

页码：18778 / 18788

页数：11

共 86 条

[1] Branched Photoswitchable Tethered Ligands Enable Ultra-efficient Optical Control and Detection of G Protein-Coupled Receptors In Vivo [J].