Factors contributing to aromatic stacking in water: Evaluation in the context of DNA
Factors contributing to aromatic stacking in water: Evaluation in the context of DNA
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DOI：
10.1021/ja9934854
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发表时间：
2000-03-15
影响因子：
15
通讯作者：
Kool, ET
中科院分区：
文献类型：
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作者：
Guckian, KM;Schweitzer, BA;Kool, ET
我们报告了在自互补DNA双链体（5 '-dXCGCGCG）（2）中使用热力学测量，其中X是未配对的天然或非天然脱氧核苷，以研究在DNA背景下稳定水性芳族堆积的力。热变性实验表明，（缺少X）由自由能形成我们研究了加入单个悬挂核苷（X）的影响，其中芳香族“碱基”是腺嘌呤、鸟嘌呤、胸腺嘧啶、胞嘧啶、吡咯、苯、4-甲基吲哚、5-硝基吲哚、三甲基苯，二氟甲苯、萘、菲和芘。发现添加这些悬挂残基可使双链体额外稳定-0.8至-3.4 kcal mol（-1）。在5 μ M DNA浓度下，T-m值范围为41.7 ℃（核心序列）至64.1 ℃（具有悬挂芘残基）。对于四种天然碱，堆积能力的大小顺序为A > G大于或等于T = C。非极性类似物一般比极性更大的天然碱堆积得更牢固。堆积的几何形状被证实在两种情况下（X =腺嘌呤和芘），通过2-D NOESY实验。研究了乙醇助溶剂对天然碱和芘堆积的影响。堆叠能力进行了比较，计算值的疏水性，偶极矩，极化率，和表面积。在一般情况下，疏水效应被发现是大于其他影响稳定堆积（静电效应，分散力），然而，天然DNA碱基被发现是依赖于疏水效应比更非极性的化合物。研究结果还指出了设计核苷类似物的策略，这些核苷类似物比天然碱基堆积得更牢固;这些化合物可能有助于稳定设计的DNA结构和复合物。
We report the use of thermodynamic measurements in a self-complementary DNA duplex (5'-dXCGCGCG)(2), where X is an unpaired natural or nonnatural deoxynucleoside, to study the forces that stabilize aqueous aromatic stacking in the context of DNA. Thermal denaturation experiments show that the core duplex (lacking X) is formed with a free energy (37 degrees C) of -8.1 kcal mol(-1) in a pH 7.0 buffer containing 1 M Na+ We studied the effects of adding single dangling nucleosides (X) where the aromatic "base" is adenine, guanine, thymine, cytosine, pyrrole, benzene, 4-methylindole, 5-nitroindole, trimethylbenzene, difluorotoluene, naphthalene, phenanthrene, and pyrene. Adding these dangling residues is found to stabilize the duplex by an additional -0.8 to -3.4 kcal mol(-1). At 5 mu M DNA concentration, T-m values range from 41.7 degrees C (core sequence) to 64.1 degrees C (with dangling pyrene residues). For the four natural bases, the order of stacking ability is A > G greater than or equal to T = C. The nonpolar analogues stack more strongly in general than the more polar natural bases. The stacking geometry was confirmed in two cases (X = adenine and pyrene) by 2-D NOESY experiments. Also studied is the effect of ethanol cosolvent on the stacking of natural bases and pyrene. Stacking abilities were compared to calculated values for hydrophobicity, dipole moment, polarizability, and surface area. In general, hydrophobic effects are found to be larger than other effects stabilizing stacking (electrostatic effects, dispersion forces); however, the natural DNA bases are found to be less dependent on hydrophobic effects than are the more nonpolar compounds. The results also point out strategies for the design nucleoside analogues that stack considerably more strongly than the natural bases; such compounds may be useful in stabilizing designed DNA structures and complexes.