电化学法研究苯磺酰类5-氟尿嘧啶衍生物与双链和G-四链DNA的相互作用  

Electrochemical investigation on the interaction of benzene sulfonyl 5-fluorouracil derivatives with double-stranded DNA and G-quadruplex DNA

作　　者：胡全[1,2] 张克军[1] 金辉乐[1] 陈锡安[1] 胡茂林[1] 王舜[1] 

机构地区：[1]温州大学纳米材料与化学重点实验室,温州325035 [2]杭州师范大学基础医学部,杭州310018

出　　处：《中国科学：化学》2012年第6期792-798,946-948,共7页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(20173133;20842007);浙江省自然科学基金(Y4080177;Y4090248);浙江省教育厅基金(Y200907715)的资助

摘　　要：本文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)63-/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非电活性苯磺酰类5-氟尿嘧啶衍生物与ds-DNA和G4-DNA的相互作用.实验结果表明:苯磺酰类5-氟尿嘧啶与ds-DNA或G4-DNA的结合常数与苯环上邻、对位取代基的得失电子能力密切相关,强吸电子基团取代有利于苯磺酰类5-氟尿嘧啶选择性结合G-四链体DNA.The interaction of double-stranded （ds） and G-quadruplex （G4） DNA with sulfonyl 5-fluorouracil derivatives （5-fluoro-l-（arylsulfonyl） pyrimidine-2,4（1H,3H）-diones） was investigated in this research, in which Au electrodes modified with ds-DNA or G4-DNAs were used as a working electrode. The investigation showed that the binding affinity with G4-DNA was significantly increased when 5-fluorouracil （5-FU） was modified with arylsulfonyl groups. The presence of strong electron-withdrawing groups on benzene sulfonyl 5-FU greatly enhanced the binding selectivity （kG4.DNA/kds.DNA）. Such results provided new insights into the potential connections between the chemical structure of drug candidates and their anticancer activities.

关 键 词：微分脉冲伏安法 双链DNA G-四螺旋DNA 苯磺酰类 5-氟尿嘧啶衍生物 抗癌活性 

分 类 号：R94[医药卫生—药剂学]