On the role of E-ring oxygen atoms in the binding of camptothecin to the topoisomerase I-DNA covalent binary complex.
On the role of E-ring oxygen atoms in the binding of camptothecin to the topoisomerase I-DNA covalent binary complex.
复制标题
E 环氧原子在喜树碱与拓扑异构酶 I-DNA 共价二元复合物结合中的作用。
DOI：
10.1016/j.bmc.2004.11.011
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Hecht,SidneyM
中科院分区：
文献类型：
--
作者：
Rahier,NicolasJ;Eisenhauer,BrianM;Gao,Rong;Thomas,ShannonJ;Hecht,SidneyM
A recent X-ray crystallographic analysis of the binding of a water soluble camptothecin analogue to the human topoisomerase I–DNA covalent binary complex has suggested the existence of some novel features in the way that camptothecin is bound to the binary complex. Four additional models based on chemical and biochemical data have also been proposed. Presently we describe S-containing analogues of camptothecin prepared on the basis of these models, and report their ability to form stable ternary complexes with human topoisomerase I, and to mediate cytotoxicity at the locus of topoisomerase I. The results indicate that replacement of the 20-OH group of CPT with a SH functionality results in diminution of the potency of CPT as a topoisomerase I poison, while replacement of the O atoms at positions 20 and 21 with S atoms results in essentially complete loss of topoisomerase I inhibitory activity.
