Silver(I)-mediated amide-to-ester transformation on unprotected peptides for protein chemical synthesis and engineering.

Silver(I)-mediated amide-to-ester transformation enables efficient peptide modification with no detectable epimerization, facilitating protein synthesis and engineering.

• Why it matters: Current methods for preparing peptide esters often involve complex steps and risk epimerization, limiting precise protein modifications essential for biomedical research and therapeutics.
• What they did: The researchers developed a chemoselective, silver(I)-mediated conversion of backbone amides into salicylaldehyde esters on unprotected peptides using an N, S-benzylidene thioacetal scaffold, demonstrated through multiple peptide syntheses and mechanistic studies.
• The result: This approach provides a versatile, efficient platform for programmable amide activation at the peptide and protein level, enabling the total synthesis of complex proteins like histones and advancing protein engineering capabilities.