BTDAzo - A Photoswitchable TRPC5 Channel Activator

Angew Chem Int Ed Engl. 2022 Jun 17. doi: 10.1002/anie.202201565. Online ahead of print.

Abstract

Photoswitchable reagents can be powerful tools for high-precision biological control. TRPC5 is a Ca2+-permeable cation channel with distinct tissue-specific roles, from synaptic function to hormone regulation. Reagents giving spatiotemporally-resolved control over TRPC5 activity may be key to understanding and harnessing its biology. Here we develop the first photoswitchable TRPC5-modulator, BTDAzo, to address this goal. BTDAzo can photocontrol TRPC5 currents in cell culture, as well as controlling endogenous TRPC5-based neuronal Ca2+ responses in mouse brain slices. BTDAzos are also the first reported azo-benzothiadiazines, an accessible and conveniently derivatised azoheteroarene with strong two-colour photoswitching. BTDAzo's TRPC5 control across relevant channel biology settings suits it for a range of dynamically reversible photoswitching studies in TRP channel biology, aiming to decipher the various biological roles of this centrally important ion channel.

Keywords: Agonists; Cation Channels; Prolactin Signalling; ligand design; photopharmacology.