BINDING OF COLCHICEINE TO TUBULIN - MECHANISMS OF LIGAND ASSOCIATION WITH TUBULIN

被引:20
作者
HASTIE, SB [1 ]
MACDONALD, TL [1 ]
机构
[1] UNIV VIRGINIA,DEPT CHEM,CHARLOTTESVILLE,VA 22901
关键词
D O I
10.1016/0006-2952(90)90002-3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Colchiceine, a closely related structural analog of colchicine possessing a C-ring tropolone, has been shown to be a potent inhibitor of microtubule assembly in vitro (I50 = 20 μM). The mechanism of inhibition is mediated through binding to tubulin (KA = 1.2 ± 0.7 × 104 M-1), although potentially not through the colchicine receptor site. Supporting the hypothesis of an alternate receptor are the observation of colchiceine binding to the isolated colchicine-tubulin complex (KA = 2.2 ± 1.0 × 104 M-1), the poor correlation between the competitive inhibition of colchicine binding (Kl = 125 μM) and the inhibition of microtubule assembly, and different structure-activity relationships for colchiceine analogs as compared to the colchicine series. © 1990.
引用
收藏
页码:1271 / 1276
页数:6
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