(R)-/(S)-2-(5-氟尿嘧啶-1-基-乙酰基)氨基-3-羟基丙酸甲酯和DNA相互作用的电化学研究

Electrochemical study of the interaction between methy(R)-/(S)-2-(5-fluorouracil-1-acetyl)amid 3-hydroxy propanoate and DNA

以自组装制得的DNA修饰电极为工作电极,采用循环伏安法以Fe(CN)63-/4-为电活性指示剂,研究了抗癌药物R型和S型的2-(5-氟尿嘧啶-1-基-乙酰基)氨基-3-羟基丙酸甲酯(简称为(R)-5FUSer和(S)-5FUSer)与DNA的相互作用。循环伏安测试结果表明:(1)体系的式电位随(R)-5FUSer和(S)-5FUSer浓度的增加呈现负移行为,可以推知(R)-5FUSer和(S)-5FUSer分子则优先通过静电结合模式与DNA发生作用;(2)5FUSer和DNA的作用与药物手性结构有关系,(S)-5FUSer和与DNA的结合平衡常数大约是(R)-5FUSer和DNA结合常数的10倍,本研究对于遗传工程中以DNA为靶标的药物设计有重要的意义。

The Interaction between DNA and（R）/（S）-2-（5-fluorouracil-1-acetyl）amido-methyl-3-hydroxy propanoate（denoted as（R）-5FUSer and（S）-5FUSer）were investigated by cyclic voltammetry.The work electrode was DNA modified electrode based on self-assembly,in which Fe（CN）63-/4-were used as electroactive indictor.The experimental results indicated：（1）the peak potential shifts negatively with the increase of the concentration of（S）-5FUSer and（R）-5FUSer,suggesting that the interaction between DNA and（S）-5FUSer or（R）-5FUSer was electrostatic,（2）The interaction of DNA with（S）-5FUSer and（R）-5FUSer had relationship with chiral drug structure.The binding equilibrium constant of（S）-5FUSer and DNA was about 10 times larger than the binding constant of（R）-5FUSer and DNA.These studies were very important for the design of DNA-argeting drugs in the hereditary engineering.