Fine-tuned photochromic sulfonylureas for optical control of beta cell Ca²⁺ fluxes.

ABSTRACT: We previously developed, synthesized and tested light-activated sulfonylureas for optical control of K_ATP channels and pancreatic beta cell activity in vitro and in vivo. Such technology relies on installation of azobenzene photoswitches onto the sulfonylurea backbone, affording light-dependent isomerization, alteration in ligand affinity for SUR1 and hence K_ATP channel conductance. Inspired by molecular dynamics simulations and to further improve photoswitching characteristics, we set out to develop a novel push-pull closed ring azobenzene unit, before installing this on the sulfonylurea glimepiride as a small molecule recipient. Three fine-tuned, light-activated sulfonylureas were synthesized, encompassing azetidine, pyrrolidine and piperidine closed rings. Azetidin

SUBMITTER: Ruckert AK 

PROVIDER: S-EPMC10947021 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature