TY - JOUR
T1 - Solid phase synthesis and circular dichroism analysis of (i -> i + 4) cyclic lactam analogues of kisspeptin
AU - Camerino, Michelle Ang
AU - Kong, David Chee Ming
AU - Chalmers, David Kenneth
AU - Thompson, Philip
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
UR - http://www.springerlink.com/content/b0250n56r4q57246/
M3 - Article
SN - 1573-3149
VL - 14
SP - 323
EP - 331
JO - International Journal of Peptide Research and Therapeutics
JF - International Journal of Peptide Research and Therapeutics
IS - 4
ER -