Bicyclic peptides: Paving the road for therapeutics of the future

Bicyclic peptides have emerged as one of the driving forces within the constrained peptide family. Due to their unique pharmaceutical attributes, peptide bicycles have garnered a reputation as promising therapeutics of the future. Combining advantages of small molecule therapeutics and biologics, the target binding qualities of this highly constrained class of molecules have been likened to those of antibodies. Over the past 5 years, the field of bicyclic peptides has advanced significantly. New bicyclic secondary peptide metabolites have been discovered in aquatic organisms and, importantly, a diverse assortment of bicyclic peptides has been synthesized de novo, exploring new chemical scaffolds. Biocompatible synthetic strategies that are suitable for large library screening platforms have helped to progress bicyclic peptides into clinical trials. This review aims to provide a comprehensive overview of the most recent progress in the field.