Differences in the topoisomerase I cleavage complexes formed by camptothecin and wakayin, a DNA-intercalating marine natural product

被引:37
作者
Kokoshka, JM
Capson, TL
Holden, JA
Ireland, CM
Barrows, LR
机构
[1] UNIV UTAH,DEPT PHARMACOL & TOXICOL,SALT LAKE CITY,UT 84112
[2] UNIV UTAH,DEPT MED CHEM,SALT LAKE CITY,UT 84112
[3] UNIV UTAH,DEPT PATHOL,SALT LAKE CITY,UT 84112
关键词
camptothecin; cleavage complex; DNA intercalator; wakayin; topoisomerase I;
D O I
10.1097/00001813-199609000-00007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Wakayin is a bispyrroloiminoquinone isolated from a Clavelina sp, ascidian by cytotoxicity directed fractionation, Like camptothecin, it has been found to inhibit the topoisomerase I catalyzed relaxation of supercoiled DNA, Wakayin enhanced cleavage complex formation at the same DNA sequences as camptothecin, Both compounds showed dose-related increases in cleavage complex formation, though wakayin's effect is attenuated at high concentrations. Wakayin is a strong DNA binder, Wakayin also differed from camptothecin in that its cleavage complexes were much less stable than those of camptothecin in 0.5 M NaCl. Again in contrast to camptothecin, wakayin stabilized cleavage complexes poorly, if at all, at 0 degrees C.
引用
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页码:758 / 765
页数:8
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