Brandenburger Y, Rose K, Bagutti C, Eberle A N
Department of Medical Biochemistry, C.M.U., Geneva, Switzerland.
J Recept Signal Transduct Res. 1999 Jan-Jul;19(1-4):467-80. doi: 10.3109/10799899909036665.
Thirteen oligomeric analogs from dimers up to a hexamer of alpha-melanocyte-stimulating hormone (alpha-MSH) were synthesized and tested on melanoma cells for their ability to bind to melanocortin type 1 (MC1) receptors and to stimulate melanin production in the cells. The peptidic oligomers were made by linking several copies of the alpha-MSH fragment analog Nle-Asp-His-[D-Phe]-Arg-Trp-Lys-NH2 to different templates through formation of oxime bonds. They were found to have binding affinities at 37 degrees C up to 8 times higher and melanogenesis-inducing activities up to 4 times higher than those of the native hormone. At 15 degrees C, one dimer showed a binding affinity 20 times higher than that of alpha-MSH. These results are discussed in terms of possible bridging of neighboring receptors which has been suggested to occur in some other systems.
合成了13种从二聚体到六聚体的α-黑素细胞刺激素（α-MSH）寡聚类似物，并在黑色素瘤细胞上测试了它们与黑素皮质素1型（MC1）受体结合以及刺激细胞中黑色素生成的能力。这些肽寡聚物是通过肟键形成将α-MSH片段类似物Nle-Asp-His-[D-Phe]-Arg-Trp-Lys-NH2的几个拷贝连接到不同模板上制成的。发现它们在37℃时的结合亲和力比天然激素高8倍，黑素生成诱导活性比天然激素高4倍。在15℃时，一种二聚体的结合亲和力比α-MSH高20倍。根据在其他一些系统中已被提出可能发生的相邻受体的桥接来讨论这些结果。
