Design and synthesis of indolo[2,3-α]quinolizin-7-one inhibitors of the ZipA-FtsZ interaction

被引：44

作者：

Jennings, LD

Foreman, KW

Rush, TS

Tsao, DHH

Mosyak, L

Li, YH

Sukhdeo, MN

Ding, WD

Dushin, EG

Kenny, CH

Moghazeh, SL

Petersen, PJ

Ruzin, AV

Tuckman, M

Sutherland, AG

机构：

[1] Wyeth Ayerst Res, Dept Med Chem, Pearl River, NY 10965 USA

[2] Biophys Enzymol, Pearl River, NY 10965 USA

[3] Infect Dis Discovery Res, Pearl River, NY 10965 USA

[4] Wyeth Ayerst Res, Dept Computat Chem, Cambridge, MA 02140 USA

[5] Wyeth Ayerst Res, Dept Biol Struct, Cambridge, MA 02140 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 06期

关键词：

antibacterials; protein-protein interaction; X-ray crystal structure; structure based design;

D O I：

10.1016/j.bmcl.2004.01.028

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The binding of FtsZ to ZipA is a potential target for antibacterial therapy. Based on a small molecule inhibitor of the ZipA-FtsZ interaction.. a parallel synthesis of small molecules was initiated which targeted a key region of ZipA involved in FtsZ binding. The X-ray crystal structure of one of these molecules complexed with ZipA was solved. The structure revealed an unexpected binding mode, facilitated by desolvation of a loosely bound surface water. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：1427 / 1431

页数：5

共 14 条

[1]

Brunger AT, 1998, ACTA CRYSTALLOGR D, V54, P905, DOI 10.1107/s0907444998003254

[2]

Denny WA, 2002, CURR MED CHEM, V9, P1655

[3] ANTIDEPRESSANTS .2. DERIVATIVES OF POLYNUCLEAR INDOLES [J].