靶向HIV-1反式激活应答RNA元件的亲吻适配体的锁核酸衍生物。

LNA derivatives of a kissing aptamer targeted to the trans-activating responsive RNA element of HIV-1.

作者信息

Lebars Isabelle, Richard Tristan, Di Primo Carmelo, Toulmé Jean-Jacques

机构信息

UMR CNRS 5144, Institut Européen de Chimie et Biologie, Pessac, France.

出版信息

Blood Cells Mol Dis. 2007 May-Jun;38(3):204-9. doi: 10.1016/j.bcmd.2006.11.008. Epub 2007 Feb 14.

DOI:10.1016/j.bcmd.2006.11.008

PMID:17300966

Abstract

We previously identified an RNA aptamer targeted to the trans-activating responsive (TAR) element of the HIV-1 genome [F. Ducongé, J.J. Toulmé, In vitro selection identifies key determinants for loop--loop interactions: RNA aptamers selective for the TAR RNA element of HIV--1. RNA 5 (1999) 1605--1614]. This hairpin aptamer binds to its target through loop-loop interactions. We derived chemically modified R06 aptamers that show improved nuclease resistance and affinity for TAR. We review here the results obtained with chimeric aptamers containing locked nucleic acid (LNA) residues. Chimeras containing 2 to 4 LNA residues in an RNA or 2'-O-methyl,RNA context display binding properties of interest and compete with the viral protein Tat for binding to TAR. NMR studies have shown that these properties are modulated by the conformation of the loop-loop helix depending on the presence of LNA residues.

摘要

我们之前鉴定出一种靶向人类免疫缺陷病毒1型（HIV-1）基因组反式激活应答（TAR）元件的RNA适配体[F. 迪孔热，J.J. 图尔梅，体外筛选确定了环-环相互作用的关键决定因素：对HIV-1的TAR RNA元件具有选择性的RNA适配体。《RNA》5（1999年）1605 - 1614页]。这种发夹状适配体通过环-环相互作用与其靶标结合。我们获得了化学修饰的R06适配体，其对核酸酶的抗性和对TAR的亲和力均有所提高。我们在此综述含有锁核酸（LNA）残基的嵌合适配体所取得的结果。在RNA或2'-O-甲基RNA背景中含有2至4个LNA残基的嵌合体表现出令人感兴趣的结合特性，并能与病毒蛋白Tat竞争结合TAR。核磁共振研究表明，这些特性受环-环螺旋构象的调节，具体取决于LNA残基的存在情况。