Stapled peptides as potential therapeutics for diabetes and other metabolic diseases

The field of peptide drug research has experienced notable progress, with stapled peptides featuring stabilized α-helical conformation, emerging as a promising field. These peptides offer enhanced stability, cellular permeability, and binding affinity and exhibit potential in the treatment of diabetes and metabolic disorders. Stapled peptides, through the disruption of protein-protein interactions, present varied functionalities encompassing agonism, antagonism, and dual-agonism. This comprehensive review offers insight into the technology of peptide stapling and targeting of crucial molecular pathways associated with glucose metabolism, insulin secretion, and food intake. Additionally, we address the challenges in developing stapled peptides, including concerns pertaining to structural stability, peptide helicity, isomer mixture, and potential side effects.