STABILITY OF TRIPLE HELICES CONTAINING RNA AND DNA STRANDS - EXPERIMENTAL AND MOLECULAR MODELING STUDIES
STABILITY OF TRIPLE HELICES CONTAINING RNA AND DNA STRANDS - EXPERIMENTAL AND MOLECULAR MODELING STUDIES
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DOI：
10.1093/nar/21.24.5547
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发表时间：
1993-12-11
影响因子：
14.9
通讯作者：
HELENE, C
中科院分区：
文献类型：
--
作者：
ESCUDE, C;FRANCOIS, JC;HELENE, C
紫外吸收分光光度法和分子模型已用于研究糖（核糖或脱氧核糖）的化学性质对三螺旋稳定性的影响。对于嘧啶.嘌呤*嘧啶基序，所有八种组合均使用由 DNA 或 RNA 组成的三条链进行了测试。糖的化学性质对三螺旋稳定性有巨大影响。对于每种双螺旋组合物，当第三链是RNA而不是DNA时，会形成更稳定的三螺旋。当多聚嘌呤序列由 RNA 组成且第三条链由 DNA 组成时，未检测到稳定的三螺旋。使用 JUMNA 程序进行的能量最小化研究表明，第三链的 2'-羟基与聚嘌呤链的磷酸盐之间的相互作用在确定三螺旋结构的相对稳定性方面发挥着重要作用，其中聚嘧啶第三链与聚嘌呤序列平行。当第三链采用相对于目标多嘌呤序列的反平行方向时，这些相互作用是不允许的，如当第三链包含G和A或G和T/U时所观察到的。我们通过足迹和凝胶阻滞实验表明，含有G和A或G和U的寡核糖核苷酸无法结合双螺旋DNA，而相应的DNA寡聚物形成稳定的三螺旋复合物。
UV-absorption spectrophotometry and molecular modeling have been used to study the influence of the chemical nature of sugars (ribose or deoxyribose) on triple helix stability. For the Pyrimidine.Purine* Pyrimidine motif, all eight combinations were tested with each of the three strands composed of either DNA or RNA. The chemical nature of sugars has a dramatic influence on triple helix stability. For each double helix composition, a more stable triple helix was formed when the third strand was RNA rather than DNA. No stable triple helix was detected when the polypurine sequence was made of RNA with a third strand made of DNA. Energy minimization studies using the JUMNA program suggested that interactions between the 2'-hydroxyl group of the third strand and the phosphates of the polypurine strand play an important role in determining the relative stabilities of triple-helical structures in which the polypyrimidine third strand is oriented parallel to the polypurine sequence. These interactions are not allowed when the third strand adopts an antiparallel orientation with respect to the target polypurine sequence, as observed when the third strand contains G and A or G and T/U. We show by footprinting and gel retardation experiments that an oligoribonucleotide containing G and A or G and U fails to bind double helical DNA, while the corresponding DNA oligomers form stable triple-helical complexes.