Cyclic Peptide
A peptide with a ring structure formed by a bond between two points in the chain. Cyclic peptides have improved stability and resistance to enzymatic degradation. Notable examples include cyclosporine, octreotide, oxytocin, and vasopressin. Cyclisation is actively exploited in peptide drug design.
Technical Context
Cyclic peptide drug design strategies: head-to-tail cyclisation (N→C backbone linkage — cyclosporine's 11 amino acid ring), disulphide cyclisation (Cys-Cys bridge — octreotide has D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol with Cys2-Cys7 bridge; oxytocin has Cys1-Cys6 bridge), lactam bridge (side chain Lys-Asp/Glu linkage), thioether bridge (lanthionine — natural in lantibiotics), and stapled peptides (hydrocarbon bridge across helix turns). Cyclic peptide advantages: constrained conformation enhances receptor binding (pre-organisation reduces entropic cost of binding), improved metabolic stability (no free termini for exopeptidases, reduced endopeptidase access), and potentially improved membrane permeability (cyclisation can mask polar groups). Rule of 5 violations are tolerated in cyclic peptides — cyclosporine (MW 1202, 7 H-bond donors) achieves oral bioavailability through chameleonic conformational flexibility.