Characterization of a putative alpha-MSH antagonist 153N-6 at melanocortin receptor subtypes by radioligand binding

This study was conducted to determine the binding properties of recently discovered, putative alpha-MSH antagonist 153N-6 peptide at melanocortin receptor subtypes. The results indicated that 153N-6 peptide can competitively inhibit [I-125]NDP-MSH binding from all the receptor subtypes investigated. The relative potency order of 153N-6 for inhibiting [I-125]NDP-MSH binding was MC(IR) (K-i 955 +/- 35.7 nM) = MC(4R) (K-i 1151 +/- 106 nM) > MG(3R) (K-i 3229 +/- 637 nM) > MG(5R) (K-i 6286 +/- 462 nM), which is different than the potency order of either NDP-MSH or a-MSH. Substitution of aspartic acid(117) and histidine(260) by alanine in melanocortin 1 receptor resulted in a 4.75-fold decrease (K-i 4541 +/- 644 nM) and an 11-fold increase (K-i 84.29 +/- 4.53 nM), respectively, in the relative potency of 153N-6 for competitively inhibiting [I-125]NDP-MSH binding.