Rapid vinyl thianthrenium tetrafluoroborate-promoted thioacid-based native chemical ligation and its applications in chemical protein synthesis.

ABSTRACT: Native chemical ligation (NCL) has emerged as the most extensively employed chemoselective reaction in chemical protein synthesis (CPS). Nevertheless, the inherently low reactivity of peptide alkyl thioesters often necessitates the use of excessive nucleophilic additives in NCL to facilitate the reaction. Herein, we describe a rapid, and additive-free peptide ligation reaction between peptide thioacid and N-terminal cysteinyl peptide without epimerization in the present vinyl thianthrenium tetrafluoroborate (VTT). VTT promotes quantitative and chemoselective activation of fully unprotected C-terminal peptide thioacids into thioester intermediates, which demonstrate exceptional reactivity, facilitating rapid NCL in an additive-free manner with high yields. This additive-free strategy is ful

SUBMITTER: Li H 

PROVIDER: S-EPMC12764823 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature