表柔比星-镁体系与DNA相互作用初步研究

表柔比星是临床上用于治疗快速增殖肿瘤的药物。本文应用紫外、荧光、圆二色、黏度、凝胶电泳等方法研究了表柔比星-Mg2+体系与DNA的作用。结果发现:在pH=7.4时,表柔比星可与Mg2+形成稳定体系。加入DNA后表柔比星-Mg2+体系的紫外吸收明显降低;Scatchard图表明表柔比星-Mg2+体系对溴化乙锭(EB)与DNA的结合为竞争性抑制;同时此体系可使DNA-EB体系荧光偏振度增大;使DNA的热变性温度(Tm)上升;黏度增大;凝胶电泳表明表柔比星-Mg2+体系对pBR322DNA有非常好的切割活性;圆二色谱法表明随着表柔比星-Mg2+体系的加入,DNA碱基间作用能迅速减弱,二级结构发生了显著的变化。综上所述:表柔比星-Mg2+体系与DNA之间为嵌插作用;且表柔比星-Mg2+体系具有更好的切割活性。这些结果,可为合理改善药效和设计新药提供依据。

Preliminary Research on the Interaction between Epirubicin-Mg2+ System and DNA

Epirubicin is used to treat the fast multiplication cancer. The interaction of Epirubicin-Mg²⁺ system with calf thymus DNA has been investigated using UV spectra, fluorescent spectra, CD, viscosity and gel electrophoresis etc. The results show that, Epirubicin can form constant system with Mg²⁺ in pH=7.4 solution. Hypochromism was observed in the UV spectra of the system in the presence of the DNA. The Scatchard plots showed competitive inhibition aganist EB binding to DNA. The relative viscosity and thermal deformation temperature of DNA increased with addition of the Epirubicin-Mg²⁺ system. The fluorescence polarization of the DNA-EB system increased with addition of the Epirubicin-Mg²⁺ system. Then the interaction of the Epirubicin-Mg²⁺ system with pBR322 was studied by the method of gel electrophoresis. The result showed that the Epirubicin-Mg²⁺ system could cleave pBR322 DNA very effectively. The energy of base pair has been weakened with addition of the Epirubicin-Mg²⁺ system. So it can be concluded that the binding mode of the Epirubicin-Mg²⁺ system with CT DNA belongs to intercalation action. This work may be usefully applied to elucidating the mechanisms of natural nucleases and drug design.