Hydrogen-abstracted adenine-thymine radicals with interesting transferable properties
Hydrogen-abstracted adenine-thymine radicals with interesting transferable properties
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DOI：
10.1021/jp0714926
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发表时间：
2007-05-17
影响因子：
3.3
通讯作者：
Schaefer, Henry F., III
中科院分区：
文献类型：
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作者：
Lind, Maria C.;Richardson, Nancy A.;Schaefer, Henry F., III
通过各种途径在DNA碱基上形成自由基会导致有害的结构改变。这样的过程对于防止健康DNA的改变是有意义的，并且相反地，对于开发用于抑制不想要的诱变DNA的复制的更精细的方法是有意义的。在目前的工作中，我们从理论上探讨的能量和结构特性的九个可能的中性自由基形成通过从腺嘌呤-胸腺嘧啶碱基对的氢提取。能量最低的自由基是由胸腺嘧啶的甲基失去一个氢原子形成的。次低能量的自由基比全局最小值高8和9 kcal mol（-1），是那些从双链DNA中连接碱基对和2-脱氧核糖的两个氮中去除氢的自由基。其他六个自由基的能量高出16至32千卡摩尔（-1）。与鸟嘌呤-胞嘧啶碱基对不同，腺嘌呤-胸腺嘧啶（A-T）在夺氢后仅表现出微小的结构变化，所有A-T衍生的自由基保持平面性。此外，两个孤立碱基（腺嘌呤和胸腺嘧啶）的自由基的能量排序在碱基对形成时被保留，尽管能量分布更广。更重要的是，从分离的腺嘌呤和胸腺嘧啶的X-H键解离能正确预测了（A-H）（中心点）-T和A-（T-H）（中心点）自由基的能量交错。这表明氢键互补碱基的添加仅略微影响键能。
The formation of radicals on DNA bases through various pathways can lead to harmful structural alterations. Such processes are of interest for preventing alteration of healthy DNA and, conversely, to develop more refined methods for inhibiting the replication of unwanted mutagenic DNA. In the present work, we explore theoretically the energetic and structural properties of the nine possible neutral radicals formed via hydrogen abstraction from the adenine-thymine base pair. The lowest energy radical is formed by loss of a hydrogen atom from the methyl group of thymine. The next lowest energy radicals, lying 8 and 9 kcal mol(-1) higher than the global minimum, are those in which hydrogens are removed from the two nitrogens that would join the base pair to 2-deoxyribose in double-stranded DNA. The other six radicals lie between 16 and 32 kcal mol(-1) higher in energy. Unlike the guanine-cytosine base pair, adenine-thymine (A-T) exhibits only minor structural changes upon hydrogen abstraction, with all A-T derived radicals maintaining planarity. Moreover, the energetic ordering for the radicals of the two isolated bases (adenine and thymine) is preserved upon formation of the base pair, though with a wider spread of energies. Even more significantly, the energetic interleaving of the (A-H)(center dot)-T and A-(T-H)(center dot) radicals is correctly predicted from the X-H bond dissociation energies of the isolated adenine and thymine. This suggests that the addition of the hydrogen-bonded complement base only marginally affects the bond energies.