磷酸基团在环丙沙星光敏损伤DNA中的作用

利用紫外-可见稳态吸收光谱, 稳态荧光发射光谱和激光光解瞬态光谱实验方法研究了磷酸基团在环丙沙星(CPX)光敏损伤DNA中的作用. 紫外-可见和稳态荧光光谱实验证实了磷酸根离子影响环丙沙星的稳态吸收和发射谱, 实验结果表明磷酸根是通过弱相互作用与环丙沙星结合. 我们还利用激光闪光光解实验分别研究了鸟苷(Gua), 脱氧鸟苷(dG)以及脱氧鸟苷酸(dGMP)对环丙沙星三线态(³CPX^*)的影响, 通过对比实验证实了在环丙沙星光敏损伤dGMP中, 由于磷酸基团的存在, 导致了环丙沙星三线态吸收峰的改变, 从而改变了光敏损伤反应的途径. 通过研究发现, 光敏损伤途径的改变是由于dGMP结构上磷酸基团通过氢键与环丙沙星结合所造成的. 最后, 根据实验结果并对比Gua, dG和dGMP的结构, 提出了一个合理的磷酸基团的作用机理.

Phosphate Base Effect on DNA Damage Photo-Induced by Ciprofloxacin

Stable and transient spectroscopic studies were conducted to investigate the influence of DNA phosphate bases in the process of DNA damage photo-induced by ciprofloxacin (CPX). The results of UV-visible and fluorescence studies confirmed that the absorption and emission properties of CPX were affected by the concentration of phosphate buffer (PB), and these results indicated that there are interactions between CPX and the phosphate anion. To investigate the relationship between the phosphate base and CPX, a comparative experiment was conducted using guanosine (Gua), 2''-deoxyguanosine (dG), and 2''-deoxyguanosine-5''c-monophosphate (dGMP). By comparative experiments, we found that the type of spectrum of CPX triplet state was changed due to the phosphate base of dGMP, hence, we concluded that the photo-damage process was changed. The effects of phosphate base of dGMP on the CPX triplet state (³CPX^*) spectrum have been investigated by laser flash photolysis methods, and the results confirmed that there are hydrogen-bonding interactions between the phosphate base of dGMP and CPX. In this study, we found that CPX and dGMP are combined together by the hydrogen bond which changed the mode of DNA damage photo-induced by CPX. Finally, based on the results obtained in this study, a rational scheme to describe the role of phosphate base playing in the DNA damage process photo-induced by CPX is proposed.