Demonstration of a Common DPhe(7)to DNal(2?)(7)Peptide LigandAntagonist Switch for Melanocortin-3 and Melanocortin-4 ReceptorsIdentifies the Systematic Mischaracterization of thePharmacological Properties of Melanocortin Peptides

摘要

Melanocortin peptides containing a 3-(2-naphthyl)-D-alanine residue in position 7 (DNal(2 ')7), reported asmelanocortin-3 receptor (MC3R) subtype-specific agonists intwo separate publications, were found to lack significant MC3Ragonist activity. The cell lines used at the University of Arizona forpharmacological characterization of these peptides, consisting ofHEK293 cells stably transfected with human melanocortin receptorsubtypes MC1R, MC3R, MC4R, or MC5R, were then obtainedand characterized by quantitative polymerase chain reaction(PCR). While the MC1R cell line correctly expressed onlyhMCR1, the three other cell lines were mischaracterized withregard to receptor subtype expression. The demonstration that a 3-(2-naphthyl)-D-alanine residue in position 7, irrespective of themelanocortin peptide template, results primarily in the antagonism of MC3R and MC4R then allowed us to search the publishedliterature for additional errors. The erroneously characterized DNal(2 ')7-containing peptides date back to 2003; thus, our analysissuggests that systematic mischaracterization of the pharmacological properties of melanocortin peptides occurred.