BPQ-DNA加合物的实验及分子动力学模拟研究

The most common type of chemical mutation involves the formation of specific adducts with DNA. Covalent modification of DNA by electrophiles is generally accepted as the initial event in chemical carcinogenesis. The aim of the present investigation is to prepare and characterize carcinogenic adducts of BPQ-deoxycytidine (dC). Detailed spectroscopic analysis can provide the structural features of specific bonding as well as the properties of the photoinduced energy and electron transfer processes between BPQ and DNA. In combination with molecular dynamics simulations, we establish the structural properties and thermodynamic aspects of adduct-containing DNA..The study of the carcinogen information have great importance to understand the mechanism of damage to DNA base at the molecular level.

DNA加合物是DNA化学损伤较为普遍的存在形式。DNA加合物就是指亲电性物质与体内DNA分子特异位点所形成的共价结合物..本项目拟制备一种新的有效致癌加合物 BPQ-deoxycytidine(dC)，研究DNA加合物结合位点及DNA结构变化，加合物分子的光谱性质-光诱导分子内电子转移和能量传递等。同时采用分子动力学模拟对DNA加合物进行模拟实验，首次观察到在光谱分析实验中无法获得的微观细节BPQ-胞嘧啶加合物结构信息，进而在分子水平上研究DNA受损机理及DNA碱基损伤形式，对肿瘤研究具有重要意义。

根据研究进展，合成了10 种BPQ-DNA 加合物，采用高效液相色谱，确定了最佳分离条件；并对它们初步进行了表征、归属和分析，取得了较为满意的结果。利用紫外可见光谱，圆二色谱，荧光光谱研究了BPQ 与脱氧鸟苷、脱氧腺苷、脱氧胞苷的加合物的光谱性质。结合光谱分析数据构建其2’-deoxycytidine加合物分子结构模型，采用密度泛函理论 B3LYP 在6-31G *水平上模拟了16 个BPQ-胞嘧啶同分异构体的几何结构。另外利用传统的吸收和线性二色性光谱，benzo[a]pyrene-7,8-dione (BPQ)在水溶液中的行为形态及与天然DNA相互作用的行为进行了研究。