Peng P J, Sahm U G, Doherty R V, Kinsman R G, Moss S H, Pouton C W
School of Pharmacy and Pharmacology, University of Bath, UK.
Peptides. 1997;18(7):1001-8. doi: 10.1016/s0196-9781(97)00035-1.
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 alpha-MSH and gamma-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 alpha-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.
迄今为止已鉴定出五种亚型的黑皮质素受体，但目前对于这些受体结合和生物活性的不同结构要求知之甚少。在本研究中，研究了C末端黑皮质素肽残基在赋予受体亚型选择性方面的作用。合成了α-MSH和γ-MSH的C末端修饰类似物，并研究了它们与MC1和MC3黑皮质素受体的相互作用。本研究进一步证明了脯氨酸12（相对于α-MSH编号）在MC1受体结合和活性方面的重要作用。尽管C末端氨基酸对MC3-R结合和活性的影响不太明显，但仍观察到其中一些对与该受体亚型的相互作用有益。
