Reversible Regulation of Succinate Dehydrogenase by Tools of Photopharmacology

J Agric Food Chem. 2022 Apr 13;70(14):4279-4290. doi: 10.1021/acs.jafc.1c08198. Epub 2022 Mar 31.

Abstract

Succinate dehydrogenase (SDH) is extremely important in metabolic function and biological processes. Modulation of SDH has been reported to be a promising therapeutic target to SDH mutations. Current measures for the regulation of SDH are scarce, and precise and reversible modulation of SDH still remains challenging. Herein, a powerful tool for reversible optical control of SDH was proposed and evaluated utilizing the technology of photopharmacology. We reported photochromic ligands (PCLs), azobenzene-pyrazole amides (APAs), that exert light-dependent inhibition effects on SDH. Physicochemical property tests and biological assays were conducted to demonstrate the feasibility of modulating SDH. In this paper, common agricultural pathogens were used to develop a procedure by which our PCLs could reversibly and precisely control SDH utilizing green light. This research would help us to understand the target-ligand interactions and provide new insights into modulation of SDH.

Keywords: SDH; azobenzene; optical control; photochromic ligands; regulation.

MeSH terms

  • Ligands
  • Mutation
  • Succinate Dehydrogenase* / metabolism

Substances

  • Ligands
  • Succinate Dehydrogenase