A Physical Organic Approach to Tuning Reagents for Selective and Stable Methionine Bioconjugation.

ABSTRACT: We report a data-driven, physical organic approach to the development of new methionine-selective bioconjugation reagents with tunable adduct stabilities. Statistical modeling of structural features described by intrinsic physical organic parameters was applied to the development of a predictive model and to gain insight into features driving the stability of adducts formed from the chemoselective coupling of oxaziridine and methionine thioether partners through Redox Activated Chemical Tagging (ReACT). From these analyses, a correlation between sulfimide stabilities and sulfimide ν (C═O) stretching frequencies was revealed. We exploited the rational gains in adduct stability exposed by this analysis to achieve the design and synthesis of a bis-oxaziridine reagent for peptide stapling. Ind

SUBMITTER: Christian AH 

PROVIDER: S-EPMC6781863 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature