Traceless Peptide Backbone Editing via Bioinspired Cysteine-to-Thiazole Conversion

Abstract Late-stage peptide modification is a powerful strategy for diversifying and expanding peptide bioactivity. Although numerous methods have been developed for peptide side-chain functionalization, chemical approaches for selective backbone editing remain scarce. Inspired by the natural enzyme-mediated conversion of cysteine residues into thiazoles during peptide biosynthesis, we developed a traceless “label-and-edit” strategy for the backbone modification of cysteine-containing peptides. This approach begins with the selective labeling of cysteine thiols using 2-bromoacetophenone, followed by photoinduced generation of a thioaldehyde/enethiol intermediate and subsequent intramolecular SH/amide cyclization to afford thiazole-containing peptides. The transformation is compatible with a broad range of synthetic and natural peptides, highlighting its potential as a versatile platform for late-stage peptide backbone editing and diversification.