Clickable tryptophan modification for late-stage diversification of native peptides.

ABSTRACT: As the least abundant residue in proteins, tryptophan widely exists in peptide drugs and bioactive natural products and contributes to drug-target interactions in multiple ways. We report here a clickable tryptophan modification for late-stage diversification of native peptides, via catalyst-free C2-sulfenylation with 8-quinoline thiosulfonate reagents in trifluoroacetic acid (TFA). A wide range of groups including trifluoromethylthio (SCF₃), difluoromethylthio (SCF₂H), (ethoxycarbonyl)difluoromethylthio (SCF₂CO₂Et), alkylthio, and arylthio were readily incorporated. The rapid reaction kinetics of Trp modification and full tolerance with other 19 proteinogenic amino acids, as well as the super dissolving capability of TFA, render this meth

SUBMITTER: Xiao Y 

PROVIDER: S-EPMC11235173 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature