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Bisphosphonic Acids Designed as Polyphosphate Kinase 2 Inhibitors

Bisphosphonic Acids Designed as Polyphosphate Kinase 2 Inhibitors. Małgorzata Burda , a Bogusław Nocek, b Artur Mucha, a Łukasz Berlicki a a Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology

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Bisphosphonic Acids Designed as Polyphosphate Kinase 2 Inhibitors

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  1. BisphosphonicAcidsDesigned as PolyphosphateKinase 2 Inhibitors Małgorzata Burda,aBogusław Nocek,b Artur Mucha,a Łukasz Berlickia a Department of Bioorganic Chemistry, Faculty of Chemistry, WrocławUniversity of Technology b The Midwest Center for Structural Genomics, Argonne National Laboratory

  2. InorganicPolyphosphate Metal ionschelator Mg2+, Zn2+, Ca2+, Fe3+ Intracellularlevel of Pi Isolation and stageremoval of toxiccations Hg+ , Cd2+, As3+ Synthesis Proc.Natl.Acad.Sci. USA, Vol. 101 (2004), No. 45, pp. 15876-15880

  3. InorganicPolyphosphate in Bacteria • Biofilm development • Quorum sensing • Stressresponse • Desiccation • Heat • UV • Starvation

  4. EnzymesAssociated with Poly P • Synthesis • Polyphosphatekinase 1 • Utilization • Endopolyphosphatase • Exopolysphosphatase • Polyphosphatekinase 2

  5. Polyphosphatekinase 2 Nucleotidessynthesis Energy storage Proc. Natl. Acad. Sci. USA, Vol. 99 (2002), No. 26, pp. 16684-16688, Proc. Natl. Acad. Sci. USA, Vol. 105 (2008), No. 46, pp. 17730-17735. • Mol. Microbiol., Vol. 74 (2009), No. 5, pp. 1187-1197

  6. Strategy Phosphoniccompounds– substrateanalogues

  7. Screening

  8. Designing

  9. Synthesis

  10. Synthesis

  11. Synthesis

  12. Synthesis

  13. Synthesis

  14. Synthesis

  15. Synthesis

  16. Synthesis

  17. Acknowledgements Thiswork was co-financed by theEuropean Union as part of theEuropeanSocial Fund

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