Peptide Backbone Cleavage and Transamidation via Thioester-to-Imide Acyl Transfer.

ABSTRACT: Cysteine thioesters are involved in a myriad of central biological transformations due to their unique reactivity. Despite their well-studied properties, we discovered an unexpected transamidation reaction of cysteine thioesters that leads to peptide backbone cleavage. S-Acylcysteine-containing peptides were found to spontaneously fragment by cleavage of the amide bond in the i-1 position to the acylated cysteine residue at pH 8-10. We present compelling evidence of a mechanism involving a central reversible thioester-to-imide acyl transfer step. The discovered transamidation reaction was found to be highly sequence dependent and to occur in peptides containing post-translational modifications (PTMs) such as cysteine S-acetylation and S-palmitoylation as well as in peptide-pe

SUBMITTER: Gless BH 

PROVIDER: S-EPMC11775684 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature