Peptides exhibit a strong affinity for their targets, with high specificity and few side effects. Cyclic peptides constitute a significant portion of marketed peptide drugs. These cyclic peptides have a larger binding surface for protein targets and can exert a wider range of pharmacological actions through protein-protein interactions. Peptide therapeutic discovery is experiencing a resurgence, especially for challenging, historically “undruggable” targets. Cyclic peptides can form stable conformations through internal hydrogen bonds, which helps them resist enzymatic degradation in the body. The “chameleon effect” allows cyclic peptides to transition between several conformations, enhancing their absorption and intracellular penetration.
Recent advancements in peptide drug discovery include the evolution of mRNA display and peptide DNA-encoded library (DEL) technology for hit generation and selection, as well as novel cyclization techniques and their combinations for peptide conformational rigidity. These developments are crucial for achieving desired binding affinity and efficacy, thereby facilitating the development of potent and orally available peptide drugs.
