[甲基酪氨酸1，甲基精氨酸7，D-亮氨酸8]-强啡肽A(1-9)-N-乙基胺和[D-半胱氨酸2-半胱氨酸5，甲基精氨酸7，D-亮氨酸8]-强啡肽A(1-9)-NH2的合成与生物活性

Synthesis and biological activity of [MeTyr1,MeArg7,D-Leu8]-dynorphin A(1-9)-NHEt and [D-Cys2-Cys5,MeArg7,D-Leu8]-dynorphin A(1-9)-NH2.

作者信息

Yoshino H, Arakawa Y, Nakazawa T, Kaneko T, Matsunaga M, Araki S, Ikeda M, Tsuchiya Y, Yamatsu K, Tachibana S

机构信息

Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1990 Aug;38(8):2274-6. doi: 10.1248/cpb.38.2274.

DOI:10.1248/cpb.38.2274

PMID:1980641

Abstract

The opioid activities of [MeTyr1]-Dyn(1-7)-NH2, [MeTyr1,D-Leu8]-Dyn(1-8)-NH2, [MeTyr1,D-Leu8]-Dyn(1-9)-NH2, [MeTyr1,D-Leu8]-Dyn(1-10)-NH2, [MeTyr1,D-Leu8]-Dyn(1-11)-NH2, and [MeTyr1,D-Leu8,12]-Dyn(1-13)-NH2 were examined in the bioassays (guinea pig ileum, mouse vas deferens and rabbit vas deferens). Because [MeTyr1,D-Leu8]-Dyn(1-9)-NH2 showed the most potent opioid activity of the peptides tested, the biological activities of two kinds of Dyn(1-9) analogues, [MeTyr1,MeArg7,D-Leu8]-Dyn(1-9)-NHEt and [D-Cys2-Cys5,MeArg7,D-Leu8]-Dyn(1-9)-NH2 were determined and compared with those of [MeTyr1,MeArg7,D-Leu8]-Dyn(1-8)-NHEt and [D-Cys2-Cys5,MeArg7,D-Leu8]-Dyn(1-8)-NHEt in the three bioassays, in the receptor binding assays, and in the mouse tail pinch test after subcutaneous administration. The results suggest that the extension of the C-terminal in the peptide chain of [MeArg7,D-Leu8]-Dyn(1-8)-NH2 analogues by Arg is ineffective for increasing the kappa-opioid activities, kappa-receptor selectivity and/or analgesic effects of the peptides.

摘要

在生物测定法（豚鼠回肠、小鼠输精管和兔输精管）中检测了[MeTyr1]-Dyn(1 - 7)-NH2、[MeTyr1,D-Leu8]-Dyn(1 - 8)-NH2、[MeTyr1,D-Leu8]-Dyn(1 - 9)-NH2、[MeTyr1,D-Leu8]-Dyn(1 - 10)-NH2、[MeTyr1,D-Leu8]-Dyn(1 - 11)-NH2和[MeTyr1,D-Leu8,12]-Dyn(1 - 13)-NH2的阿片样物质活性。由于[MeTyr1,D-Leu8]-Dyn(1 - 9)-NH2在所测试的肽中显示出最强的阿片样物质活性，因此测定了两种Dyn(1 - 9)类似物[MeTyr1,MeArg7,D-Leu8]-Dyn(1 - 9)-NHEt和[D-Cys2-Cys5,MeArg7,D-Leu8]-Dyn(1 - 9)-NH2的生物活性，并在三种生物测定法、受体结合测定法以及皮下给药后的小鼠夹尾试验中与[MeTyr1,MeArg7,D-Leu8]-Dyn(1 - 8)-NHEt和[D-Cys2-Cys5,MeArg7,D-Leu8]-Dyn(1 - 8)-NHEt的生物活性进行比较。结果表明，在[MeArg7,D-Leu8]-Dyn(1 - 8)-NH2类似物的肽链中通过精氨酸延伸C末端对于增加肽的κ-阿片样物质活性、κ-受体选择性和/或镇痛效果无效。