非硫醇法尼基转移酶抑制剂：5-芳基丙烯酰氨基二苯甲酮对芳基结合位点的利用

Non-thiol farnesyltransferase inhibitors: utilization of an aryl binding site by 5-arylacryloylaminobenzophenones.

作者信息

Mitsch Andreas, Böhm Markus, Wissner Pia, Sattler Isabel, Schlitzer Martin

机构信息

Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, D-35032 Marburg, Germany.

出版信息

Bioorg Med Chem. 2002 Aug;10(8):2657-62. doi: 10.1016/s0968-0896(02)00088-3.

DOI:10.1016/s0968-0896(02)00088-3

Abstract

We recently described a novel aryl binding site of farnesyltransferase. The 2-naphthylacryloyl residue was developed as an appropriate substituent for our benzophenone-based AAX-peptidomimetic capable of occupying this binding site, resulting in a non-thiol farnesyltransferase inhibitor with nanomolar activity. The activity of this inhibitor is readily explained on the basis of docking studies which show the 2-naphthyl residue fitting into the aryl binding site.

摘要

我们最近描述了一种法尼基转移酶的新型芳基结合位点。2-萘基丙烯酰残基被开发为我们基于二苯甲酮的AAX肽模拟物的合适取代基，该模拟物能够占据此结合位点，从而产生一种具有纳摩尔活性的非硫醇法尼基转移酶抑制剂。基于对接研究很容易解释这种抑制剂的活性，该研究表明2-萘基残基适合于芳基结合位点。

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