Fluorescent Inhibitors for IspF, an Enzyme in the Non-Mevalonate Pathway for Isoprenoid Biosynthesis and a Potential Target for Antimalarial Therapy

Designed inhibitors (like 1) of IspF, a key enzyme in the non‐mevalonate pathway for terpene biosynthesis and a potential antimalarial target, were synthesized and evaluated. Since fluorescent probes were introduced in these ligands, their affinity towards IspF from E. coli could be determined by fl...

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Published inAngewandte Chemie (International ed.) Vol. 45; no. 7; pp. 1069 - 1074
Main Authors Crane, Christine M., Kaiser, Johannes, Ramsden, Nicola L., Lauw, Susan, Rohdich, Felix, Eisenreich, Wolfgang, Hunter, William N., Bacher, Adelbert, Diederich, François
Format Journal Article
LanguageEnglish
Published Weinheim WILEY-VCH Verlag 06.02.2006
WILEY‐VCH Verlag
Wiley
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Summary:Designed inhibitors (like 1) of IspF, a key enzyme in the non‐mevalonate pathway for terpene biosynthesis and a potential antimalarial target, were synthesized and evaluated. Since fluorescent probes were introduced in these ligands, their affinity towards IspF from E. coli could be determined by fluorescence titrations. The binding modes of two ligands in ternary complexes with IspF and a ZnII ion were clarified by X‐ray analysis.
Bibliography:We gratefully acknowledge financial support for this work from the following agencies: the Hans-Fischer Gesellschaft e.V. (to J.K.), The Wellcome Trust (to W.N.H.), the Biotechnology and Biological Sciences Research Council (UK) (to W.N.H.), and InPharmatica (to W.N.H.). The authors also thank Prof. D. Arigoni and Dr. L. Kemp for help and advice. IspF=2C-Methyl-D-erythritol 2,4-cyclodiphosphate synthase.
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ArticleID:ANIE200503003
erythritol 2,4‐cyclodiphosphate synthase.
We gratefully acknowledge financial support for this work from the following agencies: the Hans‐Fischer Gesellschaft e.V. (to J.K.), The Wellcome Trust (to W.N.H.), the Biotechnology and Biological Sciences Research Council (UK) (to W.N.H.), and InPharmatica (to W.N.H.). The authors also thank Prof. D. Arigoni and Dr. L. Kemp for help and advice. IspF=2
C
D
Methyl
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ISSN:1433-7851
1521-3773
DOI:10.1002/anie.200503003