The binding mode of drugs to the TAR RNA of HIV-1 studied by electric linear dichroism
The binding mode of drugs to the TAR RNA of HIV-1 studied by electric linear dichroism
复制标题
DOI：
10.1093/nar/24.8.1460
复制
发表时间：
1996-04-15
影响因子：
14.9
通讯作者：
Hamy, F
中科院分区：
文献类型：
--
作者：
Bailly, C;Colson, P;Hamy, F
首次用电线性二色性(ELD)研究了一系列小分子与HIV-1 TAR RNA的相互作用。被测试的化合物包括脱氧核糖核酸插层药物普罗黄素和溴化乙锭，以及安非他明-4-甲酰胺脱氧核糖核酸穿线嵌入剂，以及AT特定的脱氧核糖核酸小槽结合剂netropsin、Hoechst 33258、berenil和Dari。除Netropsin外，所有病例的药物吸收带中均有负向还原的二色性信号。与前人的研究结果一致，结果表明TAR RNA可以发生经典插层和线状插层，ELD数据表明药物Hoechst 33258、贝苯尼和DAPI与TAR RNA的结合模式类似于它们在DNAGC富集区的结合模式，可能涉及插层到A型TAR RNA螺旋中。TAR RNA的宽而浅的小槽显然不能被像netropsin这样的DNA小槽结合药物所接近。ELD技术作为研究药物与TAR RNA相互作用的一种手段，似乎具有独特的价值。
For the first time, the interaction between a series of small molecules and the TAR RNA of HIV-1 has been investigated by electric linear dichroism (ELD). The compounds tested include the DNA intercalating drugs proflavine and ethidium bromide and an amsacrine-4-carboxamide DNA-threading intercalator as well as the AT-specific DNA minor groove binders netropsin, Hoechst 33258, berenil and DARI. In all cases except for netropsin, negative reduced dichroism signals were measured in the drug absorption band. in agreement with previous studies, the results indicate that both classical and threading intercalation can occur with the TAR RNA, The ELD data show that the mode of binding of the drugs Hoechst 33258, berenil and DAPI to the TAR RNA is similar to their binding mode in GC-rich regions of DNA and likely involves intercalation into the A-form TAR RNA helix. The wide and shallow minor groove of the TAR RNA is apparently not accessible to DNA minor groove binding drugs such as netropsin. The ELD technique appears uniquely valuable as a means of investigating the interaction of drugs with the TAR RNA.