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  

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

作　　者：孟晨鹏[1] 王舜[1] 张克军[1] 金辉乐[1] 陈锡安[1] 胡茂林[1] 熊静[1] 

机构地区：[1]温州大学纳米材料与化学重点实验室,温州325027

出　　处：《化学学报》2011年第10期1173-1178,共6页Acta Chimica Sinica

基　　金：国家自然科学基金(No.21073133);浙江省自然科学基金(Nos.Y4090248;Y4080177)

摘　　要：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Fe(CN)36-/4-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Fe(CN)36-/4-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,Fe(CN)36-/4-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.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.

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 

分 类 号：O646[理学—物理化学]