Goobes R, Minsky A
Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
J Biol Chem. 2001 May 11;276(19):16155-60. doi: 10.1074/jbc.M100619200. Epub 2001 Feb 13.
The thermodynamic parameters of DNA triplex formation between oligonucleotides and double-stranded DNA segments containing adenine runs (A-tracts) were investigated to explore equilibrium structural effects exerted by flanking segments upon the A-tracts. Results obtained from isothermal titration calorimetry, temperature-dependent circular dichroism (CD), and UV melting experiments indicate that A-tracts, considered as a uniquely robust and inflexible DNA motif, can be structurally perturbed by neighboring sequences in a way that significantly affects the propensity of this motif to interact with triplex-forming oligonucleotides. These contextual equilibrium effects, which depend upon the composition and location of the flanking sequences, are likely to apply not only to the interaction of A-tracts with single-stranded DNA molecules but also to interactions with drugs and proteins. As such, the current results refine the guidelines for the design of triplex-forming oligonucleotides used for antigene strategies. More generally, they substantiate the notion that significant data might be encoded by structural DNA parameters.
研究了寡核苷酸与含有腺嘌呤链（A链）的双链DNA片段之间形成DNA三链体的热力学参数，以探索侧翼片段对A链施加的平衡结构效应。等温滴定量热法、温度依赖性圆二色性（CD）和紫外熔解实验结果表明，A链作为一种独特稳定且不易弯曲的DNA基序，其结构可能会受到相邻序列的干扰，这种干扰会显著影响该基序与三链体形成寡核苷酸相互作用的倾向。这些取决于侧翼序列组成和位置的上下文平衡效应，可能不仅适用于A链与单链DNA分子的相互作用，也适用于与药物和蛋白质的相互作用。因此，目前的结果完善了用于反基因策略的三链体形成寡核苷酸的设计指南。更普遍地说，它们证实了结构DNA参数可能编码重要数据这一观点。
