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 [125I]NDP-MSH binding from all the receptor subtypes investigated. The relative potency order of 153N-6 for inhibiting [125I]NDP-MSH binding was MC1R (Ki 955 +/- 35.7 nM) = MC4R (Ki 1151 +/- 106 nM) > MC3R (Ki 3229 +/- 637 nM) > MC5R (Ki 6286 +/- 462 nM), which is different than the potency order of either NDP-MSH or alpha-MSH. Substitution of aspartic acid117 and histidine260 by alanine in melanocortin 1 receptor resulted in a 4.75-fold decrease (Ki 4541 +/- 644 nM) and an 11-fold increase (Ki 84.29 +/- 4.53 nM), respectively, in the relative potency of 153N-6 for competitively inhibiting [125I]NDP-MSH binding.
Chhajlani
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Department of Pharmaceutical Bioscience, Biomedical Centre, Uppsala, Sweden.
D000345:Affinity Labels / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D009842:Oligopeptides / Q000378:metabolism*; D011869:Radioligand Assay; D018043:Receptors, Corticotropin / Q000378:metabolism*; D044101:Receptors, Melanocortin; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism
C101068:153N-6 peptide; D000345:Affinity Labels; D009842:Oligopeptides; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-