Horvat J, Horvat S, Lemieux C, Schiller P W
Department of Organic Chemistry and Biochemistry, Rudjer Bosković Institute, Zagreb, Yugoslavia.
Int J Pept Protein Res. 1988 May;31(5):499-507. doi: 10.1111/j.1399-3011.1988.tb00908.x.
The synthesis of some [Leu5]enkephalin derivatives is described in which D-glucose has been linked to the opioid pentapeptide through the ester bond involving the carboxyl function at the C-terminal with C-1 or C-6 of the D-glucopyranose moiety. Enkephalin derivatives were assayed for opioid activity and found to be full agonists in bioassays based on inhibition of electrically evoked contractions of the guinea pig ileum (GPI) and of the mouse vas deferens (MVD). The obtained results suggest that the opioid activity of the tested glucoconjugates depend upon the ester bond position in the molecule. Whereas 1-O conjugate 5 was somewhat more potent than [Leu5]enkephalin in the GPI assay, the 6-O conjugates, with the exception of 1-O-benzyl derivative 11, were considerably less potent. All enkephalin derivatives were delta-receptor selective; in particular, the acetylated analog 8 was three times more delta-receptor selective than [Leu5]enkephalin.
本文描述了一些[亮氨酸5]脑啡肽衍生物的合成，其中D-葡萄糖通过涉及D-葡萄糖吡喃糖部分C-1或C-6与C端羧基功能的酯键与阿片肽五肽相连。对脑啡肽衍生物进行了阿片样物质活性测定，发现在基于抑制豚鼠回肠（GPI）和小鼠输精管（MVD）电诱发收缩的生物测定中，它们是完全激动剂。所得结果表明，所测试的葡萄糖缀合物的阿片样物质活性取决于分子中的酯键位置。在GPI测定中，1-O缀合物5比[亮氨酸5]脑啡肽稍强，而6-O缀合物，除了1-O-苄基衍生物11外，效力明显较低。所有脑啡肽衍生物均对δ受体具有选择性；特别是，乙酰化类似物8对δ受体的选择性是[亮氨酸5]脑啡肽的三倍。
