Selective and stable DNA base pairing without hydrogen bonds
Selective and stable DNA base pairing without hydrogen bonds
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DOI：
10.1021/ja9803310
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发表时间：
1998-06-24
影响因子：
15
通讯作者：
Kool, ET
中科院分区：
文献类型：
--
作者：
Matray, TJ;Kool, ET
芳香核碱基之间的非共价相互作用是促进双链DNA和RNA结构完整性的主要稳定力。1-3然而，核酸中的碱基配对不仅仅是氢键的结果。最近邻分析的预测成功4，以及在没有配对的情况下显示双工稳定性的“悬空基”测量5，指出了堆叠相互作用对双工完整性的重要性。然而，尽管已有关于核酸稳定性的工作，但尚不清楚氢键是否绝对需要稳定碱基对（bp）。为了测试这个问题，我们设计并合成了一系列非氢键核苷类似物来探测这些基本的相互作用。我们在此报告了第一个稳定的非氢键碱基对的发现，以及它相对于不匹配的碱基对的选择性形成。先前对非极性核苷类似物的碱基配对性质的研究几乎无一例外地表明，与天然DNA碱基的配对具有很强的不稳定性。当碱基对的两个成员都是非极性时，不稳定性有所减轻；然而，一项研究发现，相对于a - t碱基对，非极性-非极性对仍然会导致12bp双链的净失稳2.9-4.0 kcal mol−1 （Tm中9-14℃）。可能的原因是碱基之间缺乏氢键，或者在双工b型DNA中所研究的特定对的空间配合不完美。我们假设优化双相中非极性碱基对的空间配合，结合使用强堆叠基团，可能在不影响双相稳定性的情况下实现选择性配对。
Noncovalent interactions between aromatic nucleobases are the major stabilizing forces which contribute to the structural integrity of duplex DNA and RNA. 1–3 However, base pairing in nucleic acids is a consequence of more than just hydrogen bonding alone. The predictive success of nearest neighbor analysis, 4 along with “dangling base” measurements which show duplex stabilization in the absence of pairing, 5 points out the importance of stacking interactions to duplex integrity. Despite the existing work on nucleic acid stability, however, it is not yet known whether hydrogen bonds are absolutely required for stabilization of a base pair (bp). To test this question, we have designed and synthesized a series of non-hydrogenbonding nucleoside analogues to probe these fundamental interactions. 6 We report herein the finding of the first stable non-hydrogen-bonded base pair, and its selective formation relative to mismatched pairs.Prior studies on the base pairing properties of nonpolar nucleoside analogues have almost invariably shown that pairs with natural DNA bases are strongly destabilizing. 7 When both members of a base pair are nonpolar, the destabilization is lessened somewhat; 7a however, one study found that a nonpolar–nonpolar pair still resulted in net destabilization of a 12-bp duplex by 2.9–4.0 kcal mol− 1 (9–14 C in Tm) relative to an A–T base pair. 7a Possible reasons for this are the lack of hydrogen bonds between the bases or the imperfect steric fit of the specific pairs studied in the context of duplex B-form DNA. We hypothesized that optimization of the steric fit of the nonpolar base pair within the duplex, combined with the use of strongly stacking groups, might enable selective pairing without compromising duplex stability.