2-（4-甲基-1-哌嗪基甲基）苯乙酮二盐酸盐对微管蛋白烷基化的影响

The effect of 2-(4-methyl-1-piperazinylmethyl) acrylophenone dihydrochloride on the alkylation of tubulin.

作者信息

Luduena R F, Roach M C, Trcka P P, Mallevais M L, MacRae T

出版信息

Arch Biochem Biophys. 1987 Jun;255(2):453-9. doi: 10.1016/0003-9861(87)90414-0.

Abstract

2-(4-Methyl-1-piperazinylmethyl) acrylophenone dihydrochloride (MPMAP) is a novel inhibitor of microtubule assembly in vitro and in vivo whose molecular mechanism of action has not been investigated (M. L. Mallevais, A. Delacourte, I. Lesieur, D. Lesieur, M. Cazin, C. Brunet, and M. Luyckx (1984) Biochimie 66, 477-482). We have examined the effect of MPMAP on the alkylation of tubulin by iodo[14C]acetamide and N,N'-ethylenebis(iodoacetamide) (EBI). MPMAP is a very potent inhibitor of tubulin alkylation by iodo[14C]acetamide. MPMAP gives half-maximal inhibition at a concentration of 15 microM. MPMAP also inhibits the alkylation of denatured tubulin and of aldolase, implying that it reacts strongly with sulfhydryl groups. MPMAP does not, however, interfere with formation by EBI of a crosslink between cysteines 239 and 354 in the beta subunit of tubulin, suggesting that these sulfhydryls are located in a cleft in the tubulin molecule.

摘要

2-（4-甲基-1-哌嗪基甲基）苯丙烯酮二盐酸盐（MPMAP）是一种新型的体外和体内微管组装抑制剂，其分子作用机制尚未得到研究（M. L. Mallevais、A. Delacourte、I. Lesieur、D. Lesieur、M. Cazin、C. Brunet和M. Luyckx（1984年），《生物化学》66卷，477 - 482页）。我们已经研究了MPMAP对碘代[14C]乙酰胺和N，N'-亚乙基双（碘乙酰胺）（EBI）使微管蛋白烷基化的影响。MPMAP是碘代[14C]乙酰胺使微管蛋白烷基化的一种非常有效的抑制剂。MPMAP在浓度为15微摩尔时产生半数最大抑制作用。MPMAP还抑制变性微管蛋白和醛缩酶的烷基化，这意味着它与巯基强烈反应。然而，MPMAP并不干扰EBI在微管蛋白β亚基的半胱氨酸239和354之间形成交联，这表明这些巯基位于微管蛋白分子的一个裂隙中。