Late-Stage Diversification of Native Tryptophan-containing Peptides and Peptide Drugs through Nitrogen Atom Insertion

Peptide drugs are a powerful modality in modern drug dis-covery. Synthetic methods that enable the late-stage diversifi-cation of native peptides through amino acid-specific modifi-cations are thus in high demand. In this work, we demonstrate the epimerization-free, site-selective late-stage diversification of tryptophan-containing native peptides through nitrogen atom insertion in solution. The direct application of this rapid and straightforward method to structurally complex peptide drugs underscores the broader potential of atom insertion reactions in drug discovery beyond small molecules.