表柔比星-铜体系与DNA作用的光谱和电化学法研究  

Study on the Interaction between Epirubicin-Cu System and DNA by Spectroscopic and Electrochemical Methods

作　　者：席小莉[1] 杨曼曼[1] 杨频[1] 

机构地区：[1]山西大学分子科学研究所化学生物学与分子工程教育部重点实验室,太原030006

出　　处：《化学学报》2008年第10期1181-1186,共6页Acta Chimica Sinica

基　　金：国家自然科学基金(No.20601018)资助项目.

摘　　要：表柔比星是临床上广泛用于治疗增殖很快的肿瘤.应用紫外、荧光、黏度、循环伏安等方法研究了表柔比星及表柔比星-Cu2+体系与DNA的作用.结果发现:在pH=7.4时,表柔比星可与Cu2+形成稳定体系.加入DNA后表柔比星-Cu2+体系的紫外吸收明显降低;Scatchard图表明表柔比星-Cu2+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;循环伏安法表明DNA的加入使得表柔比星及表柔比星-Cu2+体系的式量电位正移;凝胶电泳表明表柔比星-Cu2+体系对pBR322 DNA有非常好的水解切割活性.综合以上结果得出:表柔比星及表柔比星-Cu2+体系与DNA之间均为嵌插作用;表柔比星-Cu2+体系具有更好的水解切割活性.这些结果可为合理改善药效、降低抗癌药物毒性和设计新药提供依据。The interaction of epirubicin-Cu system with calf thymus DNA has been investigated using UV spectra, fluorescent spectra, viscosity, cyclic voltammetry, etc. Hypochromism was observed in the UV spectra of the system in the presence of the DNA. The Scatchard plots showed competitive inhibition aganist ethidium bromide （EB） binding to DNA. The relative viscosity and thermal deformation temperature of DNA increased with addition of the epirubicin-Cu system. The fluorescence polarization of the DNA-EB system increased with addition of the epirubicin-Cu system. Determination of cyclic voltammetry showed that the DNA made the epirubicin-Cu formal potential positively shift. Then the interaction of the epirubi- cin-Cu system with pBR322 DNA was studied by the method of gel electrophoresis, The result showed that the epirubicin-Cu system could cleave pBR322 DNA very effectively. So it can be concluded that the binding mode of the epirubicin-Cu system with CT DNA belongs to intercalation action.

关 键 词：表柔比星-Cu^2+体系 CT DNA Scatchard图 

分 类 号：Q523[生物学—生物化学]