CHLOROACETATES OF 2-DEMETHYLTHIOCOLCHICINE AND 3-DEMETHYLTHIOCOLCHICINE - SPECIFIC COVALENT INTERACTIONS WITH TUBULIN WITH PREFERENTIAL LABELING OF THE BETA-SUBUNIT

被引：15

作者：

GROVER, S ^{[1
]}

BOYE, O ^{[1
]}

GETAHUN, Z ^{[1
]}

BROSSI, A ^{[1
]}

HAMEL, E ^{[1
]}

机构：

[1] NIDDKD,STRUCT BIOL LAB,BETHESDA,MD 20892

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1992年 / 187卷 / 03期

关键词：

D O I：

10.1016/0006-291X(92)90451-P

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We synthesized two chemically reactive A ring modified analogs of colchicine, 2-chloroacetyl-2-demethylthiocolchicine (2-CTC) and 3-chloroacetyl-3-demethylthiocolchicine (3-CTC). Both are similar to colchicine as inhibitors of tubulin polymerization and act as competitive inhibitors of colchicine binding (apparent Ki values, 3 μM). [14C]-labeled 2-CTC and 3-CTC bound to tubulin at 37°C but not at 0°C, and bound drug formed covalent bond(s) with tubulin. The binding and covalent reactions were inhibited by podophyllotoxin. About 60% of the bound 3-CTC rapidly formed a covalent bond with tubulin. With 2-CTC the covalent reaction was slower than the binding reaction, and only one-third of the bound 2-CTC reacted covalently with tubulin. The ratio of radiolabel in β-tubulin to that in α-tubulin was about 4:1 with both 2-CTC and 3-CTC. © 1992.

引用

页码：1350 / 1358

页数：9

共 17 条

[1] IDENTIFICATION OF THE CYSTEINE RESIDUE OF BETA-TUBULIN ALKYLATED BY THE ANTIMITOTIC AGENT 2,4-DICHLOROBENZYL THIOCYANATE, FACILITATED BY SEPARATION OF THE PROTEIN SUBUNITS OF TUBULIN BY HYDROPHOBIC COLUMN CHROMATOGRAPHY [J].