Theoretical evaluation of a bulky <i>ortho</i>-thioalkyl-azobenzene as an alternative to photocontrol structural cytotoxic effects of metal-free and disulfide oxidized hSOD1 in pathogenesis of ALS.

ABSTRACT: This study presents a novel photopharmacological strategy to mitigate the cytotoxic effects of apo-hSOD1^S-S, a misfolded protein implicated in neurodegenerative diseases. Using quantum chemical calculations and molecular dynamics simulations, we demonstrate that ortho-thio-substituted azobenzene photoswitches (ortho-TABPs) can be employed to precisely modulate the dynamics of the crucial electrostatic loop (EL) in apo-hSOD1^S-S. We establish that larger ortho-S-alkyl substituents on the ortho-TABP enhance its redox stability, favouring the cis conformation through the modulation of the position of the n → π* transition. This stability is crucial for operation within the reducing cellular environment. Furthermore, we demonstrate

SUBMITTER: Galaz-Araya C 

PROVIDER: S-EPMC11931720 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature