Cyclisation
The process of forming a ring structure within a peptide chain by creating a bond between two points in the molecule. Cyclic peptides often have improved stability, receptor selectivity, and resistance to enzymatic degradation compared to their linear counterparts.
Technical Context
Cyclisation occurs through several mechanisms: head-to-tail (N-terminus to C-terminus backbone linkage), side chain-to-side chain (e.g. disulphide bonds between cysteines, lactam bridges between lysine and glutamate), or backbone-to-side chain connections. Cyclic peptides resist enzymatic degradation better than linear peptides because they lack free terminal ends recognised by exopeptidases, and their constrained conformation reduces endopeptidase access. Cyclosporine (11 amino acids) is a cyclic peptide essential to immunosuppressive therapy. Octreotide, lanreotide, and pasireotide are cyclic somatostatin analogues. The cyclic scaffold is actively exploited in modern peptide drug design programmes.