铂类抗肿瘤药物ZD0473与双链及单链DNA作用差异的理论研究  

Theoretical Study on the Differences of Interactions Between Pt-Complex Anticancer Drug ZD0473 and Double and Single Strand DNA

作　　者：贾木欣[1] 曲雯雯[1] 陈光巨[1] 刘若庄[1] 

机构地区：[1]北京师范大学化学系

出　　处：《高等学校化学学报》2004年第8期1481-1484,M005,共5页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金 (批准号 :2 0 2 710 0 9;2 0 2 3 10 10 );国家重点基础研究发展计划(批准号 :G2 0 0 0 0 7810 1);教育部重点科学基金;回国人员科学基金资助

摘　　要：用分子力学与量子化学相结合的 MM/uff//HF/lanl2 dz方法及单独的密度泛函方法探讨了新型铂类抗肿瘤药物 ( ZD0 473 )与碱基序列相同的双链及单链 DNA片段几何结构、相互作用及电子结构方面的异同 .结果表明 ,虽然药物分子都能与单、双链 DNA形成稳定的复合物 ,但双链复合物与 DNA形成的配位键比单链复合物稍强 ,氨中的氢与 O6G8间形成的氢键更强 ,甲基吡啶所造成的位阻效应更高 。cis-Amminedichloro(2-methylpyridine)platinum(Ⅱ),also known as ZD0473,is a new Pt-complex anticancer drug rationally designed to circumvent the cisplatin resistance of some tumor cells. The MM/uff//HF/lanl2dz method combining molecular mechanics with quantum chemistry and the solely density function method B3LYP/lanl2dz//6-31G * are used to investigate the geometry,interaction and electron structure differences between the adducts of this drug and the same base sequence single and double strand DNA in this paper. The results show that even though the drug molecule can form stable adducts with both the single and the double strand DNA,the double strand adduct has such advantages over the single one as the drug forms comparatively stronger coordinate bonds between Pt and the guanines and better hydrogen bond between the amine and the O6G 8 and the picoline has a higher stereo hindrance which further decreases the drug resistance of tumor cells.

关 键 词：ZD0473 MM/uff//HF/lanl2dz DNA片段 

分 类 号：O641[理学—物理化学]