Binding and biological activity of C-terminally modified melanocortin peptides: A comparison between their actions at rodent MC₁ and MC₃ receptors

Five subtypes of melanocortin receptors have to date been identified, but to date little is known about the different structural requirements for binding and biological activity at these receptors. In this study, the role of C-terminal melanocortin peptide residues in imparting selectivity for the receptor subtypes was examined. C-terminally modified analogues of α-MSH and γ-MSH were synthesized and their interaction with MC₁ and MC₃ melanocortin receptors was investigated. This study provides further evidence for an important role of proline 12 (numbering with respect to α-MSH) for binding and activity at the MC₁ receptor. Although the influence of C-terminal amino acids on binding and activity at MC₃-R was less marked, some of them were nevertheless observed to be beneficial for the interaction with this receptor subtype.