Expanding the horizon of the thymine isostere biochemistry: unique cyclobutane dimers formed by photoreaction between a thymine and a toluene residue in the dinucleotide framework.
Expanding the horizon of the thymine isostere biochemistry: unique cyclobutane dimers formed by photoreaction between a thymine and a toluene residue in the dinucleotide framework.
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扩大胸腺嘧啶等排生物化学的视野：通过胸腺嘧啶和二核苷酸框架中的甲苯残基之间的光反应形成独特的环丁烷二聚体。
DOI：
10.1002/chem.201200816
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Li,Lei
中科院分区：
文献类型：
--
作者：
Liu,Degang;Zhou,Yan;Pu,Jingzhi;Li,Lei
取代甲苯基被认为是胸腺嘧啶残基的同分异构体。它们可以被DNA聚合酶识别，就好像它们是胸腺嘧啶一样。由于芳香环的稳定结构，这些甲苯衍生物通常对自由基加成物（包括[2+2]光环加成物）是惰性的，通常用作自由基反应的溶剂。令人惊讶的是，在将甲苯加入二核苷酸框架后，我们发现紫外线激发的胸腺嘧啶残留物很容易通过[2+2]光加成反应与甲苯部分二聚。此外，甲苯部分的反应位点不是环丁烷嘧啶二聚体中常见的C5 <s:1> C6键，而是C4 <s:2> C5或C3 <s:2> C4。这样的反应模式表明，在堆叠结构中，是这些键中的一个，而不是C5 <s:1> C6，接近胸腺嘧啶C5 <s:2> C6键。在DNA双链中发现了类似的结构特征，胸腺嘧啶被2,4‐二氟甲苯取代。我们的研究结果表明，虽然取代的甲苯基部分非常接近胸腺嘧啶残基的大小和形状，但它们更疏水的性质决定了它们在DNA碱基上的堆叠与天然胸腺嘧啶残基不同，并可能导致双链DNA的局部构象变化。
Substituted toluenyl groups are considered as close isosteres of the thymine residue. They can be recognized by DNA polymerases as if they were thymine. These toluene derivatives are generally inert toward radical additions, including the [2+2] photo‐cycloadditions, due to the stable structure of the aromatic ring and are usually used as solvents for radical reactions. Surprisingly, after incorporating toluene into the dinucleotide framework, we found that the UV excited thymine residue readily dimerizes with the toluenyl moiety through a [2+2] photo‐addition reaction. Furthermore, the reaction site on the toluenyl moiety is not the C5C6 bond, as commonly observed in cyclobutane pyrimidine dimers, but the C4C5 or C3C4 instead. Such a reaction pattern suggests that in the stacked structure, it is one of these bonds, not the C5C6, that is close to the thymine C5C6 bond. A similar structural feature is found in DNA duplex with a thymine replaced by a 2,4‐difluorotoluene. Our results argue that although the substituted toluenyl moieties closely mimic the size and shape of the thymine residue, their more hydrophobic nature determines that they stack on DNA bases differently from the natural thymine residue and likely cause local conformational changes in duplex DNA.