Towards Gram-negative antivirulence drugs: New inhibitors of HldE kinase |
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Authors: | Nicolas Desroy François Moreau Sophia Briet Géraldine Le Fralliec Stephanie Floquet Lionel Durant Vanida Vongsouthi Vincent Gerusz Alexis Denis Sonia Escaich |
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Institution: | MUTABILIS SA, 102 Avenue Gaston Roussel, 93230 Romainville, France |
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Abstract: | Gram-negative bacteria lacking heptoses in their lipopolysaccharide (LPS) display attenuated virulence and increased sensitivity to human serum and to some antibiotics. Thus inhibition of bacterial heptose synthesis represents an attractive target for the development of new antibacterial agents. HldE is a bifunctional enzyme involved in the synthesis of bacterial heptoses. Development of a biochemical assay suitable for high-throughput screening allowed the discovery of inhibitors 1 and 2 of HldE kinase. Study of the structure–activity relationship of this series of inhibitors led to highly potent compounds. |
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