Emerging Strategies to Access Peptide Macrocycles from Genetically Encoded Polypeptides

Macrocyclic peptides have emerged as attractive molecular scaffolds for the development of chemical probes and therapeutics. In this synopsis, we highlight contemporary strategies to access peptide macrocycles from ribosomally produced polypeptides. Challenges that have been tackled in this area involve orchestrating the desired macrocyclization process in the presence of unprotected polypeptide precursors and expanding the functional space encompassed by these molecules beyond that of canonical amino acid structures. Applications of these methodologies for the discovery of bioactive molecules are also discussed.