Evidence for alternate points of attachment for alpha-MSH and its stereoisomer [Nle4, D-Phe7]-alpha-MSH at the melanocortin-1 receptor.

作者: P.A. Frandberg , R. Muceniece , P. Prusis , J. Wikberg , V. Chhajlani

DOI: 10.1006/BBRC.1994.2067

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摘要: The molecular basis for the alpha-melanocyte stimulating hormone (alpha-MSH) stereoselectivity was studied by examining ligand binding to site specific mutants of melanocortin 1 receptor (MC1R). amino acids Asp117, Phe179, His209 and His260 were targeted mutation alanine as they are conserved in family. Expression wild type MC1R COS-7 cells revealed that affinities alpha-MSH (L-isomer) reduced 267 fold D117-->A mutant 132 H260-->A mutant. In contrast, affinity [Nle4, D-Phe7]-alpha-MSH (NDP-MSH; D-isomer) remain unchanged between mutants. Moreover, also displayed reduction L-isomers all other melanocortic peptides examined. Thus, single third sixth transmembrane segments results display MC1R. addition, these data represent first evidence different epitopes on a G-protein coupled peptide stereoisomers, both which shown be potent agonists.

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