DMPK Research of Cyclic Peptides

Peptides exhibit a strong affinity for their targets, high specificity, and few side effects. Among them, cyclic peptides constitute a significant portion of the 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. Additionally, 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 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 the desired binding affinity and efficacy, thereby facilitating the creation of potent and orally available peptide drugs.