Cyclic peptides are now a modality in modern drug development. The constrained structure confers higher stability, enhanced cell permeability, and binding than their linear counterparts. However, synthesizing cyclic peptides requires unique synthetic know-how.
Cyclic peptides contain a cyclic ring structure in their polypeptide chain. Linking the desired end of functional groups in the peptide sequence allows the formation of a ring structure.
Three general approaches allow the formation of the ring structure in cyclic peptides:
(1) Disulfide bonds between two or several cysteine residues form cyclic structures.
(2) Generating an amide bond between the two ends of the peptide creates a ring structure called head-to-tail cyclization.
(3) The formation of an amide bond connected to at least one side chain residue in the peptide creates the ring structure.