SIOC English
化学学报
高级检索

化学学报 ›› 2011, Vol. 69 ›› Issue (10): 1173-1178. 上一篇    下一篇

研究论文

2-(5-氟尿嘧啶-1-乙酰基)氨基-1,5-戊二酸二甲酯手性异构体与双链/G-四链体DNA相互作用的电化学研究

孟晨鹏, 王舜*, 张克军, 金辉乐*, 陈锡安, 胡茂林, 熊静   

  1. (温州大学纳米材料与化学重点实验室 温州 325027)
  • 投稿日期:2010-09-30 修回日期:2011-01-10 发布日期:2011-05-28
  • 通讯作者: 王舜 E-mail:shunwang@wzu.edu.cn
  • 基金资助:

    基于纳米信号放大技术和组合电化学法研究G-四螺旋DNA与配体分子的相互作用;基于柔性基底的金微电极阵列的制备及其在G-四螺旋DNA靶向分子高通量筛选中的应用;具有识别靶向药物分子功能的纳米单层有机-无机复合膜的制备及应用

Electrochemical Study on the Interactions between Enantiomer of 2-(5-Fluorouracil-1-acetyl)amido-1,5-dimethyl Glutarate and Double-stranded/G-quadruplex DNA

MENG Chen-Peng, WANG Shun, ZHANG Ke-Jun, JIN Hui-Le, CHEN Xi-An, HU Mao-Lin, XIONG Jing   

  1. (Nano-materials & Chemistry Key Laboratory, Wenzhou University, Wenzhou 325027)
  • Received:2010-09-30 Revised:2011-01-10 Published:2011-05-28
  • Contact: WANG Shun E-mail:shunwang@wzu.edu.cn

PDF

1162

被引次数

13

以自组装法制得的双链DNA(ds-DNA)和G-四链体DNA(G4-DNA)修饰的金电极为工作电极, 以 为电活性指示剂, 采用循环伏安法和微分脉冲伏安法研究了R和S型2-(5-氟尿嘧啶-1-乙酰基)氨基-1,5-戊二酸二甲酯(简称为(R)-5FUGlu和(S)-5FUGlu)与ds-DNA和G4-DNA相互作用. 实验结果表明: (1)与5-氟尿嘧啶(5-FU)相反, (R)-5FUGlu或(S)-5FUGlu导致 在Au/ds-DNA和Au/G4-DNA修饰电极上的峰电位呈现负移行为|(2)随着5-FU, (R)-或(S)-5FUGlu浓度的增加, 在上述修饰电极上的峰电流均呈现下降现象, 且峰电流的下降值△Ip的倒数与药物浓度的倒数呈现良好的线性关系|(3)运用Langmuir公式计算获得5-FU, (S)-5FUGlu和(R)-5FUGlu与ds-DNA的结合常数分别为6.16×103, 0.42×103和0.58×103 L•mol－1, 而与G4-DNA 的结合常数分别为0.78×103, 2.60×103和5.29×103 L•mol－1|(4) (R)-5FUGlu和(S)-5FUGlu在浓度为10－4, 10－6, 10－8 mol•L－1时对HL-60肿瘤细胞生长的抑制率分别为55.8和2.8, 12.8和1.5以及5.9和0.6, 这与(R)-5FUGlu比(S)-5FUGlu分子具有更强的靶向结合G4-DNA能力相吻合.

关键词: G-四链体DNA, 5-氟尿嘧啶二肽衍生物, 微分脉冲伏安法, 手性异构体, 抗癌活性

The interaction between 2-(5-fluorouracil-1-acetyl) amido-1,5-dimethyl glutarate enantiomer and DNA have been investigated via cyclic and differential pulse voltammetry, in which double-stranded DNA (ds-DNA) or G-quadruplex DNA (G4-DNA) modified Au electrode was used as the working electrode while was employed as the electroactive indicator. Our investigation indicates that: (1) As opposed to the influence of 5-fluorouracil (5-FU), (S)-5FUGlu and (R)-5FUGlu caused the peak potential of at Au/ds-DNA and Au/G4-DNA electrodes shift negatively|(2) 5-FU, (S)-5FUGlu and (R)-5FUGlu all caused the peak current of at the above modified electrodes to decrease, in which the inverse of current change exhibited a linear relationship with the inverse of reagent concentration|(3) Utilizing Langmuir equation the binding constants of 5-FU, (S)- and (R)-5FUGlu with ds-DNA are found to be 6.16×103, 0.42×103 and 0.58×103 L•mol－1, respectively, whereas the binding constants of 5-FU, (S)- and (R)-5FUGlu with G4-DNA are 0.78×103, 2.60×103 and 5.29×103 L•mol－1|and (4) the inhibition rates of (R)- and (S)-5FUGlu on tumor cell line HL-60 are, respectively, 55.8 and 2.8, 12.8 and 1.5, and 5.9 and 0.6 at the concentrations of 10－4, 10－6 and 10－8 mol•L－1, which is consistent with the observed tendency that (R)-5FUGlu and G4-DNA have a stronger binding affinity than that of (S)-5FUGlu.

Key words: G-quadruplex DNA, 5-fluorouracil-dipeptide derivatives, differential pulse voltammetry, enantiomer, anti-tumor activity

中图分类号: