Design of cyclic peptides with agonist activity at melanocortin receptor-4.
A series of cyclic pentapeptides, c(His-D-Phe-Arg-Trp-Z) (Z=omega-amino acid), were prepared and biologically evaluated. The effects of increasing alkyl chain length of omega-amino acid on the functional activities and the receptor binding affinities for human melanocortin receptors (hMC-Rs) were studied. Compound 2 was an agonist for hMC-4R with an EC50 value of 15.4 nM, which was 4.7 times more potent than that of alpha-MSH. Compound 2 also showed a 4.3-fold higher hMC-4R selectivity over hMC-1R, thus providing us with information concerning size and chemical structure of the lactam ring for the development of the agonist with hMC-4R selectivity.
Odagami
Takenao
T
Research Center, Pharmaceutical R&D Division, Asahi Kasei Pharma Corporation, Izunokuni 410-2321, Japan.
Tsuda
Yuko
Y
Kogami
Yuji
Y
Kouji
Hiroyuki
H
Okada
Yoshio
Y