Solid Phase Synthesis and Circular Dichroism Analysis of (i → i + 4) Cyclic Lactam Analogues of Kisspeptin |
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| Authors: | Michelle A Camerino David C M Kong David K Chalmers Philip E Thompson |
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| Institution: | (1) Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia;(2) Department of Pharmacy Practice, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia |
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| Abstract: | The α-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 α-helical activity in aqueous buffer, in comparison to the linear native peptide, which showed
no helical character. |
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| Keywords: | Cyclic peptide Lactam bridge Kisspeptin Alpha helix Solid phase peptide synthesis Circular dichroism |
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