表柔比星-铁体系与DNA作用的光谱和电化学法研究

Study on the Interaction between Epirubicin-Fe^(2+) System and DNA by Spectroscopic and Electrochemical Methods

表柔比星是临床上广泛用于治疗增殖很快肿瘤的药物.应用紫外、荧光、园二色、黏度、循环伏安等方法研究了表柔比星及表柔比星-Fe2+体系与DNA的作用.结果发现,在pH=7.4时表柔比星可与Fe2+形成稳定体系,加入DNA后表柔比星-Fe2+体系的紫外吸收明显降低.Scatchard图表明,表柔比星-Fe2+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-Fe2+体系的式量电位正移.园二色谱法表明,随着表柔比星-Fe2+体系的加入,DNA碱基间作用能迅速减弱.综合以上结果得出:表柔比星及表柔比星-Fe2+体系与DNA之间均为嵌插作用,而且表柔比星-Fe2+体系具有比单纯表柔比星更好的嵌插效果.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.

Epirubicin is used to treat the fast multiplication cancer. The interaction of Epirubicin-Fe2＋ system with calf thymus DNA has been investigated using UV spectra, fluorescent spectra, CD, viscosity and cyclic voltammetry etc. The results show that Epirubicin can form constant system with Fe2＋ 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-Fe2＋ system. The fluores-cence polarization of the DNA-EB system increased with addition of the Epirubicin-Fe2＋ system. Determi-nation of cyclic voltammetry showed that the DNA made the Epirubicin-Fe2＋ formal potential positively shift. The energy of base pair has been weakened with addition of the Epirubicin-Fe2＋ system. So it can be concluded that the binding mode of the Epirubicin-Fe2＋ system with CT DNA belongs to intercalation action. This work may be usefully applied to elucidating the mechanisms of natural nucleases and drug design.