期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 58, 期 14, 页码 4531-4535出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201813110
关键词
agonism; dynamic modulation; H3R; photopharmacology; VUF15000
资金
- Netherlands Organisation for Scientific Research (NWO) [718.014.002]
Spatiotemporal control over biochemical signaling processes involving G protein-coupled receptors (GPCRs) is highly desired for dissecting their complex intracellular signaling. We developed sixteen photoswitchable ligands for the human histamine H-3 receptor (hH(3)R). Upon illumination, key compound 65 decreases its affinity for the hH(3)R by 8.5-fold and its potency in hH(3)R-mediated G(i) protein activation by over 20-fold, with the trans and cis isomer both acting as full agonist. In real-time two-electrode voltage clamp experiments in Xenopus oocytes, 65 shows rapid light-induced modulation of hH(3)R activity. Ligand 65 shows good binding selectivity amongst the histamine receptor subfamily and has good photolytic stability. In all, 65 (VUF15000) is the first photoswitchable GPCR agonist confirmed to be modulated through its affinity and potency upon photoswitching while maintaining its intrinsic activity, rendering it a new chemical biology tool for spatiotemporal control of GPCR activation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据