Definition
A cyclic peptide has its chain joined into a ring rather than having free ends. Cyclisation can link the N- and C-termini head-to-tail through an amide bond, connect side chains to each other or to a terminus, or rely on a disulfide bridge between cysteines. Ring closure reduces conformational flexibility, which can raise receptor selectivity and binding affinity, and it removes the free termini that exopeptidases attack, often improving stability. Natural examples include cyclosporin and gramicidin S; synthetic examples include octreotide and the melanocortin peptide bremelanotide. Head-to-tail cyclisation can be confirmed by mass spectrometry because it removes one molecule of water, about 18 Da, relative to the linear precursor.