Characterization of disulfide (cystine) oxidation by HOCl in a model peptide: Evidence for oxygen addition, disulfide bond cleavage and adduct formation with thiols.

Characterization of disulfide (cystine) oxidation by HOCl in a model peptide: Evidence for oxygen addition, disulfide bond cleavage and adduct formation with thiols.
Free Radic Biol Med. 2020 May 01;:
Authors: Karimi M, Crossett B, Cordwell SJ, Pattison DI, Davies MJ
Abstract
Disulfide bonds play a key role in stabilizing proteins by cross-linking secondary structures. Whilst many disulfides are effectively unreactive, it is increasingly clear that some disulfides are redox active, participate in enzymatic reactions and/or regulate protein function by allosteric mechanisms. Previously (Karimi et al., Sci. Rep. 2016, 6, 38752) we have shown that some disulfides react rapidly with biological oxidants due to favourable interactions with available lone-pairs of electrons. Here we present data from kinetic, mechanistic and product studies for HOCl-mediated oxidation of a protected nine-amino acid model peptide containing a N- to C-terminal disulfide bond. This peptide reacts with HOCl with k2 1.8 × 106 M-1 s-1, similar to other highly-reactive disulfide-containing compounds. With low oxidant excesses oxidation yields multiple oxidation products from the disulfide, with reaction predominating at the N-terminal Cys to give sulfenic, sulfinic and sulfonic acids, and disulfide bond cleavage. Limited oxidation occurs, with higher oxidant excesses, at Trp and His residues to give mono- and di- (for Trp) oxygenated products. Site-specif...

Source: Free Radical Biology and Medicine - April 30, 2020 Category: Biology Authors: Karimi M, Crossett B, Cordwell SJ, Pattison DI, Davies MJ Tags: Free Radic Biol Med Source Type: research