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[化学核糖核酸酶。2. 基于具有不同正电荷的二氮杂双环[2.2.2]辛烷的核糖核酸酶模拟物的设计与水解特性]

[Chemical ribonucleases. 2. Design and hydrolytic properties RNase mimetics based on diazabicyclo[2.2.2]octane with various positive charges].

作者信息

Zenkova M A, Vlasov A V, Konevets D A, Sil'nikov V N, Giege R, Vlasov V V

机构信息

Novosibirsk Institute of Bioorganic Chemistry, Siberian Division, Russian Academy of Sciences, Novosibirsk, Russia.

出版信息

Bioorg Khim. 2000 Sep;26(9):679-85.

Abstract

A procedure was proposed allowing one to synthesize RNA mimics on the basis of conjugates of diazabicyclo[2.2.2]octane with imidazole bearing a varying number of positive charges (nDm series, where n is the number of positive charges at neutral pH, m is the code of an imidazole-containing fragment of the catalytic domain: 1, histamine; 2, histidine methyl ester). The hydrolytic activity of six compounds of this series was studied under physiological conditions using in vitro transcript of human mitochondrial tRNA(Lys) as a substrate. It was shown that the rate of RNA hydrolysis with nDm conjugates rises with an increase in the number of positive charges: an approximately 30-fold acceleration of hydrolysis was observed with an increase in the total charge of the construct from +2 to +4.

摘要

提出了一种方法,可基于二氮杂双环[2.2.2]辛烷与带有不同数量正电荷的咪唑的共轭物合成RNA模拟物(nDm系列,其中n是中性pH下的正电荷数量,m是催化结构域含咪唑片段的代码:1,组胺;2,组氨酸甲酯)。使用人线粒体tRNA(Lys)的体外转录本作为底物,在生理条件下研究了该系列六种化合物的水解活性。结果表明,nDm共轭物的RNA水解速率随正电荷数量的增加而提高:随着构建体总电荷从+2增加到+4,观察到水解加速约30倍。

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