Synthesis and antibacterial activity of mechanism-based inhibitors of KDO8P synthase and DAH7P synthase |
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Authors: | Grison Claude Petek Sylvain Finance Chantal Coutrot Philippe |
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Institution: | Laboratoire de Chimie Organique Biomoléculaire, UMR CNRS 7565, Institut Nancéien de Chimie Moléculaire, Université Henri Poincaré, Nancy 1, BP 239, F-54506 Vandoeuvre-lès-Nancy, France. cgrison@univ-montp2.fr |
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Abstract: | KDO8PS (3-deoxy-D-manno-2-octulosonate-8-phosphate synthase) and DAH7PS (3-deoxy-D-arabino-2-heptulosonate-7-phosphate synthase) are attractive targets for the development of new anti-infectious agents. Both enzymes appear to proceed via a common mechanism involving the reaction of phosphoenolpyruvate (PEP) with arabinose 5-phosphate or erythrose-4-phosphate, to produce the corresponding ulosonic acids, KDO8P and DAH7P, respectively. The synthesis of new inhibitors closely related to the supposed tetrahedral intermediate substrates for the enzymes is described. The examination of the antibacterial activity of these derivatives is reported. |
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Keywords: | KDO8P synthase DAH7P synthase Lipopolysaccharide Shikimate pathway 2-Glycosyl-2-hydroxyphosphonopropanoic acid Antibacterial activity |
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