Thionoesters: A Native Chemical Ligation-Inspired Approach to Cysteine-Triggered H₂S Donors.

ABSTRACT: Native chemical ligation (NCL) is a simple, widely used, and powerful synthetic tool to ligate N-terminal cysteine residues and C-terminal α-thioesters via a thermodynamically stable amide bond. Building on this well-established reactivity, as well as advancing our interests in the chemical biology of reactive sulfur species including hydrogen sulfide (H₂S), we hypothesized that thionoesters, which are constitutional isomers of thioesters, would undergo a similar NCL reaction in the presence of cysteine to release H₂S under physiological conditions. Herein, we report mechanistic and kinetic investigations into cysteine-mediated H₂S release from thionoesters. We found that this reaction proceeds with high H₂S-releasing efficiency (∼80%) and with a

SUBMITTER: Cerda MM 

PROVIDER: S-EPMC6504978 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature