Glossary
Cyclic Peptide
A cyclic peptide is closed into a ring through a covalent bond. The four ring types, and why cyclisation boosts protease resistance and selectivity.
In a cyclic peptide, a covalent bond links parts of the backbone or side chains so that the molecule forms a ring. There are four recognised ways to close it: head-to-tail, connecting the N- and C-termini; side chain to side chain, usually via a disulfide bridge or a lysine–glutamate lactam; head-to-side-chain; and side-chain-to-tail.
What ring closure achieves
The consequences are threefold. Resistance to proteases increases, since exopeptidases require a free end to begin cutting and a head-to-tail ring has none. Conformational entropy drops, so the molecule adopts a binding-ready shape more often, which usually improves affinity as well as selectivity. And certain cyclic peptides reach surprising membrane permeability by tucking their backbone hydrogen bonds inside the ring — the feature that lets cyclosporine be absorbed orally despite its large size.
Relevant catalogue examples are the disulfide-closed rings of oxytocin and somatostatin, and the conformationally restricted Melanotan II set against its more flexible relatives. Ring closure belongs to the same toolbox as PEGylation and DAC — each prolongs useful lifetime, but cyclisation works by withstanding cleavage rather than by delaying clearance. Compare linear peptides; see how sequences are written.
Related terms
half-life · analog