Peptides having potent antagonist and agonist bioactivities at melanocortin receptors

摘要

Cyclic lactam peptides, seven amino acids in length, having D- 2'- naphthylalanine (D-2'-Nal) or D-para-iodo-phenylalanine D-(p-I)Phe at position 4 of the peptide provided potent and specific antagonists of the two neural melanocortin receptors and of the peripheral receptor. In particular, the peptide ##STR1## was found to be a potent antagonist of the MC3 and MC4 receptors with partial agonist activity, and a full agonist of the MC1 and MC5 receptors; the peptide ##STR2## was found to be a potent antagonist of the MC3 and MC4 receptors with partial agonist activity. Both peptides have antagonist activities in the classical frog skin bioassay for pigmentation at the MC1 receptor.