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

Abstract This study was conducted to determine the binding properties of recently discovered, putative α-MSH antagonist 153N-6 peptide at melanocortin receptor subtypes. The results indicated that 153N-6 peptide can competitively inhibit [ 125 I]NDP-MSH binding from all the receptor subtypes investigated. The relative potency order of 153N-6 for inhibiting [ 125 I]NDP-MSH binding was MC 1R ( K i 955 ± 35.7 n M ) = MC 4R ( K i 1151 ± 106 n M ) > MC 3R ( K i 3229 ± 637 n M ) > MC 5R ( K i 6286 ± 462 n M ), which is different than the potency order of either NDP-MSH or α-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 n M ) and an 11-fold increase ( K i 84.29 ± 4.53 n M ), respectively, in the relative potency of 153N-6 for competitively inhibiting [ 125 I]NDP-MSH binding.