Cyclic melanotropins. 5. Importance of the C-terminal tripeptide (Lys-Pro-Val)

Publisher Website
Google Scholar
Abstract
It was previously reported that [Cys4,Cys10]-.alpha.-MSH and Ac-[Cys4,Cys10]-.alpha.-MSH4-13-NH2 were superpotent melanotropins. Ac-[Cys4,Cys10]-.alpha.-MSH4-10-NH2, which constitutes the cyclic analog of the putative active site sequence-Met4-Glu5-His6-Phe7-Arg8-Trp9-Gly10- of .alpha.-MSH, was much less active. In the present investigation the contribution of the Lys11 and Pro12 residues of the C-terminal carboxamide tripeptide-Lys11-Pro12-Val13-NH2 to the potency of Cys4,Cys10 containing cyclic melanotropins was studied. Ac-[Cys4,Cys10]-.alpha.-MSH4-11-NH2 was less potent than .alpha.-MSH in the frog and lizard skin bioassays and the mouse S-91 (Cloudman) melanoma adenylate cyclase assay but more potent than Ac-[Cys4,Cys10]-.alpha.-MSH4-10-NH2 in the 3 assays studied. Ac-[Cys4,Cys10]-.alpha.-MSH4-12-NH2 was considerably more potent than the cyclic 4-11 melanotropin and was equipotent or even slightly more potent than [Cys4,Cys10]-.alpha.-MSH and Ac-[Cys4,Cys10]-.alpha.-MSH4-13-NH2 over the linear portion of the dose-response in all 3 bioassays. Lys11 and Pro12 but to a lesser extent Val13 of the C-terminal tripeptide sequence evidently contributes to the potency of the cyclic melanotropins. The further substitution of a D-Phe7 for the L-Phe7 residue into the cyclic 4-12 analog resulted in a highly potent compound Ac-[Cys4,D-Phe7,Cys10]-.alpha.-MSH4-12-NH2 that exhibited highly prolonged biological activity.

This publication has 3 references indexed in Scilit: