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Etudes in silico et expérimentale de la DXR & synthèse de D- et L-GAP énantiomériquement purs

Abstract : This thesis concerns the study of the 2 first enzymes of the MEP pathway: DXS and DXR. The MEP pathway permits the biosynthesis of isoprénoïdes in most bacteria, including pathogenic one. As it is not present in human, enzymes of MEP pathway are effective targets in the research of new antimicrobial drugs. The objective was to advance the development of new antimicrobiotic compounds. We used computational tools: molecular docking and molecular dynamics simulations coupled with an MM/PBSA approach. We were able to identify residues that contribute significantly to the ligand binding in the DXR active site. These results were used to guide the conception of new inhibitor models, such as bisubstrates, biligands and α,α-difluoro phosphonates, two of which were synthetized. We also developed a synthesis method to obtain L- and D-GAP as enantiomerically pure molecules. The goal was to study the enantiospecificity of DXS to its substrate, D-GAP.
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Fanny Krebs. Etudes in silico et expérimentale de la DXR & synthèse de D- et L-GAP énantiomériquement purs. Autre. Université de Strasbourg, 2016. Français. ⟨NNT : 2016STRAF059⟩. ⟨tel-01672058v2⟩

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