Peptide drugs are a powerful modality in modern drug discovery. Synthetic methods that enable the late-stage diversification of native peptides through amino acid-specific modifications are thus in high demand. In this work, we demonstrate the epimerization-free, chemoselective 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.

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Chemical & Engineering News (C&EN): Keeping you up to date with the chemistry news that matters most. Published by the American Chemical Society.

Chemical & Engineering News (C&EN): Keeping you up to date with the chemistry news that matters most. Published by the American Chemical Society.

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Single-atom skeletal editing has recently emerged as a powerful strategy for the direct diversification of the heterocyclic cores of various compounds. Yet, methods that enable monocycle-to-bicycle tr...