Solid phase synthesis and circular dichroism analysis of (i -> i + 4) cyclic lactam analogues of kisspeptin

The alpha-helix is one of the most common secondary structure elements adopted by proteins and is commonly stabilized in synthetic peptides via the formation of a covalent side-chain to side-chain lactam bridge. In this study, we explored the application of various side-chain to side-chain lactam bridges to helix stabilization of kisspeptin analogues, an interesting candidate for ligand-based drug discovery with potential as anti-metastatic agents. We successfully synthesised a series of Asp/Lys, Lys/Asp, Glu/Lys and Lys/Glu lactams, finding peptide (1) cyclo(4,8)Tyr-Asn-Trp-Glu-Ala-Phe-Gly-Lys-Arg-Phe-NH2, to exhibit characteristic alpha-helical activity in aqueous buffer, in comparison to the linear native peptide, which showed no helical character.