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

ABSTRACT: The limitations of classical drugs have spurred the development of covalently tethered photoswitchable ligands to control neuromodulatory receptors. However, a major shortcoming of tethered photopharmacology is the inability to obtain optical control with an efficacy comparable with that of the native ligand. To overcome this, we developed a family of branched photoswitchable compounds to target metabotropic glutamate receptors (mGluRs). These compounds permit photo-agonism of G_i/o-coupled group II mGluRs with near-complete efficiency relative to glutamate when attached to receptors via a range of orthogonal, multiplexable modalities. Through a chimeric approach, branched ligands also allow efficient optical control of G_q-coupled mGluR5, which we use to probe the spat

SUBMITTER: Acosta-Ruiz A 

PROVIDER: S-EPMC7216301 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature