The cyclic peptide has been recognized as an important class of drug molecules and biochemical tools. The advantages of cyclic peptides over linear peptides include conformational rigidity that decreases the entropy of binding to target molecules and a diverse sequence of peptide residues that can provide binding motifs for various receptors.
In addition, a cyclic peptide can be more resistant to hydrolytic degradation due to the lack of both amino and carboxyl termini. Cyclic peptides are also more stable and have improved permeability in comparison to linear peptides, making them suitable for drug delivery. A number of cyclic peptides are currently under development and clinical use, including linaclotide (2012) and plecanatide (2017) for treating chronic idiopathic constipation by stimulating the cystic fibrosis transmembrane conductance regulator (CFTR) protein to activate guanylate cyclase on the luminal surface of gut epithelial cells.
In order to achieve a functionally closed cyclic peptide, the amino and carboxyl groups need to be protected from reactions that would form undesirable amide or disulfide bond links. Consequently, a large variety of deprotection and oxidation conditions have been developed.
In addition, the cyclic peptide can be screened for cellular uptake using phage display technology. For example, a cyclic peptide library generated from the self-defense peptide tachyplesin of horseshoe crabs was screened for Caco-2 cell permeability and found to have good permeability. Similarly, a cyclic peptide mimetic of monoclonal antibody specific for the p185HER2/neu growth factor receptor was shown to bind to the receptor in a complex with an RGD ligand, suggesting that the cyclic peptide may function as a small-molecule inhibitor of cancer cell growth.