Optical control of endogenous receptors and cellular excitability using targeted covalent photoswitches.

ABSTRACT: Light-regulated drugs allow remotely photoswitching biological activity and enable plausible therapies based on small molecules. However, only freely diffusible photochromic ligands have been shown to work directly in endogenous receptors and methods for covalent attachment depend on genetic manipulation. Here we introduce a chemical strategy to covalently conjugate and photoswitch the activity of endogenous proteins and demonstrate its application to the kainate receptor channel GluK1. The approach is based on photoswitchable ligands containing a short-lived, highly reactive anchoring group that is targeted at the protein of interest by ligand affinity. These targeted covalent photoswitches (TCPs) constitute a new class of light-regulated drugs and act as prosthetic molecules that photoco

SUBMITTER: Izquierdo-Serra M 

PROVIDER: S-EPMC4961765 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature