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The structure of model and peptide disulfides markedly affects their reactivity and products formed with singlet oxygen.
- Source :
-
Free Radical Biology & Medicine . Oct2023, Vol. 207, p320-329. 10p. - Publication Year :
- 2023
-
Abstract
- Disulfide bonds are critical structural elements in proteins and stabilize folded structures. Modification of these linkages is associated with a loss of structure and function. Previous studies have reported large variations in the rate of disulfide oxidation by hypohalous acids, due to stabilization of reaction intermediates. In this study we hypothesized that considerable variation (and hence selective oxidation) would occur with singlet oxygen (1O 2), a key intermediate in photo-oxidation reactions. The kinetics of disulfide-mediated 1O 2 removal were monitored using the time-resolved 1270 nm phosphorescence of 1O 2. Stern-Volmer plots of these data showed a large variation (∼103) in the quenching rate constants k q (from 2 × 107 for α-lipoic acid to 3.6 × 104 M−1s−1 for cystamine). The time course of disulfide loss and product formation (determined by LC-MS) support a role for 1O 2 , with mono- and di-oxygenated products detected. Elevated levels of these latter species were generated in D 2 O- compared to H 2 O buffers, which is consistent with solvent effects on the 1O 2 lifetime. These data are interpreted in terms of the intermediacy of a zwitterion [–S+(OO−)–S–], which either isomerizes to a thiosulfonate [–S(O) 2 –S–] or reacts with another parent molecule to give two thiosulfinates [–S(O)–S-]. The variation in quenching rates and product formation are ascribed to zwitterion stabilization by neighboring, or remote, lone pairs of electrons. These data suggest that some disulfides, including some present within or attached to proteins (e.g., α-lipoic acid), may be selectively modified, and undergo subsequent cleavage, with adverse effects on protein structure and function. [Display omitted] • Kinetics of disulfide-mediated 1O 2 removal monitored using time-resolved phosphorescence. • Rate constants for 1O 2 removal show a marked variation with structure (103 -107 M−1 s−1). • 5-membered ring disulfides (lipoic acid, lipoamide) react more rapid than linear disulfides. • LC-MS analyses show formation of mono- (thiosulfinate) and di-oxygenated (thiosulfonate) products. • Protein disulfides may show similar variable reactivity and selective oxidation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08915849
- Volume :
- 207
- Database :
- Academic Search Index
- Journal :
- Free Radical Biology & Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 171922228
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2023.08.024