8-氧-2'-去氧鸟嘌呤核苷水解机理的理论研究

Theoretic study on hydrolysis mechanism of 8-oxo-2′-deoxyguanosine

本文用计算化学的方法研究了有单个水分子参与的8-氧-2'-去氧鸟嘌呤核苷(8-oxodG)的N-糖苷键水解反应机理.研究结果表明,水分子有两个进攻方向,即水分子可以从去氧核糖糖环的上方和下方进攻C1'并且8-氧鸟嘌呤碱基的O8原子和N9原子都可以摘取去氧糖环的Ha2'.因此,8-oxodG与单个水分子作用的水解反应有四条不同的反应通道,且每条反应通道都包括两步,都形成类双氢呋喃中间体.O8原子摘取去氧糖糖环Ha2'的反应的两条反应途径的第一步的活化能相近,约为41.98kcal/mol;而N9原子摘取去氧糖糖环Ha2'的反应的两条反应途径的第一步的活化能也相近,约为47.31kcal/mol.碱基上O8原子摘取去氧核糖糖环Ha2'的反应的两条反应途径更具有优势.

The calculational chemistry method has been used to study the hydrolysis mechanism for glycosidic bond of 8-oxodG involving a single water molecule in this article. The result indicates that the water molecule can attack the C1’ atom from two orientations, above or under the deoxyribose ring of the 8-oxodG, and both O8 and N9 atoms in the base of 8-oxodG can abstract Ha-2＇ atom of the deoxyribose ring. So, there are four different pathways for the hydrolysis reaction of 8-oxodG and single water molecule. Every pathway consists of two steps involving the formation of a dihydrofurane-like intermediate. The activation energies of the first steps in the two pathways abstracting the Ha-2＇ by O8 atom are similar,which are about 41.98 kcal/mol . While, the activation energies of the first steps in the two pathways abstracting the Ha-2＇ by N9 atom are similar, which are also about 47.31 kcal/mol. The two pathways abstracting the Ha-2＇ by O8 atom of the base have a bigger advantage .