The anticancer agent ellipticine unwinds DNA by intercalative binding in an orientation parallel to base pairs
The anticancer agent ellipticine unwinds DNA by intercalative binding in an orientation parallel to base pairs
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DOI：
10.1107/s0907444905015404
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发表时间：
2005-07-01
影响因子：
2.2
通讯作者：
Coll, M
中科院分区：
文献类型：
--
作者：
Canals, A;Purciolas, M;Coll, M
椭圆藤碱是一种天然植物产物，已被发现是一种强大的抗癌药物。尽管尚不清楚，但其作用机制被认为主要基于DNA嵌入和/或抑制拓扑异构酶II。许多实验数据表明，嵌入的基础上堆叠相互作用沿着主要的碱基对轴，但替代的结合模式已被提出，特别是椭圆形衍生物。椭圆藤碱与6 bp寡核苷酸复合的1.5埃分辨率结构揭示了其结合模式，并能够详细分析药物对DNA的扭曲作用。
Ellipticine is a natural plant product that has been found to be a powerful anticancer drug. Although still unclear, its mechanism of action is considered to be mainly based on DNA intercalation and/or the inhibition of topoisomerase II. Many experimental data suggest an intercalation based on stacking interactions along the major base-pair axis, but alternative binding modes have been proposed, in particular for ellipticine derivatives. The 1.5 angstrom resolution structure of ellipticine complexed to a 6 bp oligonucleotide unveils its mode of binding and enables a detailed analysis of the distorting effects of the drug on the DNA.