SELECTIVITY OF [PHE-I-7], [ALA(6)], AND [D-ALA(4),GLN(5),TYR(6)] SUBSTITUTED ACTH(4-10) ANALOGS FOR THE MELANOCORTIN RECEPTORS

We tested [Ala(6)]ACTH(4-10) and [Phe-I-7]ACTH(4-10) (putative MC rece ptor antagonists), [D-Ala(4),Gln(5),Tyr(6)] ACTH(4-10) (BIM22015), and ACTH(4-10) with radioligand binding using transiently expressed human MC1, MC3, MC4, and MC5 receptors. [Phe-I-7]ACTH(4-1O) had higher affi nity for the MC3 MC4, and MC5 receptors but lower for the MC1 compared to ACTH(4-10). [Ala(6)]ACTH(4-10) did not bind the MC1 receptor but h ad highest affinity for the MC4 receptor. The data indicate that the H is(6) has a specially important role in binding to the MC1 receptor. T he BIM 22015 did not bind to these MC receptor subtypes, which indicat es that the neurotrophic and myotrophic properties that are attributed to this peptide are mediated by some other receptor. (C) 1997 Elsevie r Science Inc.