Cyclic peptide is an attractive drug class for the development of novel therapeutic agents. Their structural rigidity allows for a large binding surface which enhances peptide affinity toward target molecules. Cyclization also improves peptide pharmacokinetics by reducing energy barriers for passive diffusion and active transport, thus increasing the effective molecule volume (Sohrabi et al., 2020). Cyclization of peptides can also provide an extra level of control in the design and modification of their functional properties.
Cyclified peptides can be designed to interact with the protein ligand-binding surfaces of a wide range of receptors and ligands. The cyclic structure can increase binding affinity and selectivity toward a target compared to linear peptides, while the structural rigidity of a peptide can reduce steric effects on receptor interactions (Park et al., 2000). The RGD peptide is an example of a cyclic peptide that can act as a potent and selective agonist for the p185HER2/neu tyrosine kinase receptor (Park et al., 2000).
Cyclic peptides can also be used as wound healing agents and cytoprotectants. For example, an optimized cyclic heptapeptide CyRL-QN15 has been shown to enhance the rate of wound closure in diabetic mice. It was loaded onto a zinc alginate hydrogel dressing that was applied to full-thickness wounds. The peptide was found to promote the proliferation of keratinocytes and fibroblasts, and decrease the amount of inflammatory cells. It was also able to prevent ischemic reperfusion injury. In addition, a cyclic peptide derived from Isaria japonica was found to induce astrocyte proliferation and protect the central nervous system against neurodegeneration (Ishiguro et al., 2021).