AI Article Synopsis
- Developed sixteen photoswitchable ligands for the human histamine H receptor (hH R) to control its biochemical signaling processes using light.
- Compound 65 effectively reduces its affinity for hH R and its potency in activating G proteins upon illumination, showing rapid modulation of receptor activity in real-time experiments.
- Ligand 65 (VUF15000) is the first confirmed photoswitchable GPCR agonist that allows spatiotemporal control over GPCR activation while maintaining its intrinsic activity, making it a valuable tool for research.
Article Abstract
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 receptor (hH R). Upon illumination, key compound 65 decreases its affinity for the hH R by 8.5-fold and its potency in hH R-mediated G 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 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563694 | PMC |
| http://dx.doi.org/10.1002/anie.201813110 | DOI Listing |
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