Selective inhibition of type-I geranylgeranyltransferase in vitro and in whole cells by CAAL peptidomimetics
Selective inhibition of type-I geranylgeranyltransferase in vitro and in whole cells by CAAL peptidomimetics
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DOI：
10.1016/s0968-0896(97)10040-2
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发表时间：
1998-03-01
影响因子：
3.5
通讯作者：
Hamilton, AD
中科院分区：
文献类型：
--
作者：
Qian, YM;Vogt, A;Hamilton, AD
在本文中，我们描述了作为GGT酶-I抑制剂的CAAL肽模拟物家族的合成。这些抑制剂在香叶基香叶基化蛋白的关键CAAL羧基末端序列中缺乏中心二肽AA，并且对GGT酶-I的选择性高于FT酶。在整个细胞中，这些化合物是非常有效的抑制剂的加工的香叶基香叶基化蛋白Rap 1A，而不影响法尼基化蛋白H-Ras。一种衍生物GGTI-298通过阻断细胞周期的G（1）期来抑制细胞分裂。(C)1998爱思唯尔科技有限公司版权所有。
In this paper we describe the synthesis of a family of CAAL peptidomimetics as GGTase-I inhibitors. These inhibitors lack the central dipeptide AA in the key CAAL carboxy terminal sequence of geranylgeranylated proteins and are more selective for GGTase-I over FTase. In whole cells, these compounds are very potent inhibitors of the processing of the geranylgeranylated protein Rap1A without affecting the farnesylated protein H-Ras. One derivative, GGTI-298, inhibited cell division by blocking cells in the G(1) phase of the cell cycle. (C) 1998 Elsevier Science Ltd. All rights reserved.