A cyclic peptide is one whose backbone or side chains are joined by a covalent bond to form a ring. Four closure types are recognised: head-to-tail, joining N- and C-termini; side-chain to side-chain, most commonly a disulfide bridge or a lactam between lysine and glutamate; head-to-side-chain; and side-chain-to-tail.
Why cyclisation matters in peptide research
Three effects follow. Protease resistance improves, because exopeptidases need a free terminus to attack and a head-to-tail ring offers none. Conformational entropy falls, so the molecule spends more time in a binding-competent shape, which typically raises both affinity and selectivity. And some cyclic peptides achieve unusual membrane permeability by shielding backbone hydrogen bonds inside the ring — the property that makes cyclosporine orally absorbed despite its size.
Catalogue-relevant examples include the disulfide-closed rings of oxytocin and somatostatin, and the constrained Melanotan II compared against its more flexible relatives. Cyclisation is a design strategy in the same family as PEGylation and DAC — all extend useful lifetime, but cyclisation does so by resisting cleavage rather than by slowing clearance. Compare linear peptides; see how sequences are written.