Nonphosphate inhibitors of IspE protein, a kinase in the non-mevalonate pathway for isoprenoid biosynthesis and a potential target for antirnalarial therapy

被引：41

作者：

Hirsch, Anna K. H.

Lauw, Susan

Gersbach, Philipp

Schweizer, W. Bernd

Rohdich, Felix

Eisenreich, Wolfgang

Bacher, Adelbert

Diederich, Francois

机构：

[1] Laboratorium für Organische Chemie, ETH Zürich, Hünggerberg, HCI

[2] Lehrstuhl für Organische Chemie und Biochemie, Technische Universität München, 85748 Garching

来源：

CHEMMEDCHEM | 2007年 / 2卷 / 06期

关键词：

D O I：

10.1002/cmdc.200700014

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

IspE kinase inhibitors. The first inhibitors for the kinase IspE, an enzyme of the non-mevalonate pathway, are presented. The nonphosphate based inhibitors avoid binding to the ATP site but instead occupy the substrate site and a small, newly detected hydrophobic subpocket at the active site of IspE. With appropriate filling of this pocket, competitive inhibition constants K ic in the upper nanomolar range are measured. (Figure Presented) © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

收藏

页码：806 / 810

页数：5

相关论文

共 33 条

[11]

Hirsch A. K. H., 2007, ANGEW CHEM, V119, P342

[12] Phosphate recognition in structural biology [J].

Hirsch, Anna K. H. ;

Fischer, Felix R. ;

Diederich, Francois .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2007, 46 (03) :338-352

[13] Starving the malaria parasite:: Inhibitors active against the aspartic proteases plasmepsins I, II, and IV [J].

Hof, F ;

Schütz, A ;

Fäh, C ;

Meyer, S ;

Bur, D ;

Liu, J ;

Goldberg, DE ;

Diederich, F .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2006, 45 (13) :2138-2141

[14]

HOF F, UNPUB

[15] Nonmevalonate terpene biosynthesis enzymes as antiinfective drug targets: Substrate synthesis and high-throughput screening methods [J].

Illarionova, Victoria ;

Kaiser, Johannes ;

Ostrozhenkova, Elena ;

Bacher, Adelbert ;

Fischer, Markus ;

Eisenreich, Wolfgang ;

Rohdich, Felix .

JOURNAL OF ORGANIC CHEMISTRY, 2006, 71 (23) :8824-8834

[16] Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs [J].

Jomaa, H ;

Wiesner, J ;

Sanderbrand, S ;

Altincicek, B ;

Weidemeyer, C ;

Hintz, M ;

Türbachova, I ;

Eberl, M ;

Zeidler, J ;

Lichtenthaler, HK ;

Soldati, D ;

Beck, E .

SCIENCE, 1999, 285 (5433) :1573-1576

[17] Program DYNAFIT for the analysis of enzyme kinetic data: Application to HIV proteinase [J].

Kuzmic, P .

ANALYTICAL BIOCHEMISTRY, 1996, 237 (02) :260-273

[18] Studies on the nonmevalonate pathway:: conversion of 4-(cytidine 5′-diphospho)-2-C-methyl-D-erythritol to its 2-phospho derivative by 4-(cytidine 5′-diphospho)-2-C-methyl-D-erythritol kinase [J].

Kuzuyama, T ;

Takagi, M ;

Kaneda, K ;

Watanabe, H ;

Dairi, T ;

Seto, H .

TETRAHEDRON LETTERS, 2000, 41 (16) :2925-2928

[19] Biosynthesis of terpenoids:: YchB protein of Escherichia coli phosphorylates the 2-hydroxy group of 4-diphosphocytidyl-2C-methyl-D-erythritol [J].

Lüttgen, H ;

Rohdich, F ;

Herz, S ;

Wungsintaweekul, J ;

Hecht, S ;

Schuhr, CA ;

Fellermeier, M ;

Sagner, S ;

Zenk, MH ;

Bacher, A ;

Eisenreich, W .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (03) :1062-1067

[20] Interactions with aromatic rings in chemical and biological recognition [J].

Meyer, EA ;

Castellano, RK ;

Diederich, F .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (11) :1210-1250

← 1 2 3 4 →