Université de Lyon, Institut de Chimie de Lyon, CNRS, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
Org Biomol Chem. 2013 May 14;11(18):3038-45. doi: 10.1039/c3ob40280k.
The presence of two vicinal single-nucleotide oxidative lesions constitutes a pitfall case for DNA repair. Quantum mechanics calculations are performed to elucidate the formation of peroxyl-bridged adducts, where a purine and a pyrimidine base become covalently tethered. A dispersion-corrected density functional theory (DFT-D) screening along the 32 possible adducts built by a combination of the four different nucleobases outlines that guanine is a better tandem partner than adenine, in line with experimental data. In contrast, cytosine and thymine have an overall comparable reactivity as revealed by a highly localized spin density. For a given purine and pyrimidine combination, our computational approach also sketches some differences concerning the syn vs. anti configurations and the orientation strand.
两个相邻的单核苷酸氧化损伤的存在构成了 DNA 修复的一个陷阱案例。我们进行了量子力学计算，以阐明过氧桥接加合物的形成，其中嘌呤和嘧啶碱基共价连接。通过组合四个不同碱基构建的 32 种可能加合物的弥散校正密度泛函理论（DFT-D）筛选表明，鸟嘌呤是比腺嘌呤更好的串联伙伴，这与实验数据一致。相比之下，胞嘧啶和胸腺嘧啶的整体反应性相当高，这是由高度局域化的自旋密度揭示的。对于给定的嘌呤和嘧啶组合，我们的计算方法还描绘了一些关于顺式与反式构型以及取向链的差异。
