Visible Light Induced Mukaiyama Reagent Promoted Desulfurative Modification of Peptides and Proteins with Nucleotides.

ABSTRACT: Site-selective modification of peptides and proteins serves as a powerful tool for biological research and therapeutic development. We present a visible-light-driven stereoretentive peptide/protein-nucleotide conjugation via Cys desulfurization, enabling C5-selective coupling with 6-azauracil nucleosides through stable C-C bond formation. Using Mukaiyama reagent (N-alkyl-2-halopyridinium) activation under visible light (400 or 420-430 nm), this method generates configurationally stable Ala radicals while avoiding the detrimental side effects associated with UVA irradiation. The disulfide-compatible system preserves native stereochemistry and accommodates diverse substrates including oligonucleotides, functionalized nucleosides, and drug conjugates in good yields. Biocompatible reduc

SUBMITTER: Wang M 

PROVIDER: S-EPMC12670305 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature