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Design, Synthesis and Evaluation of Novel Inhibitors of CT and DosR

Zhang:Design, Synthesis and Evaluation
Autor: Guangtao Zhang
Verfügbarkeit: Auf Lager.
Artikelnummer: 1193700
ISBN / EAN: 9783639309690

Verfügbarkeit: sofort lieferbar

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Zusatzinformation

  • Autor:
  • Verlag: VDM Verlag Dr. Müller
  • ISBN / EAN: 9783639309690
  • Bindung: Taschenbuch

Produktbeschreibung

Infectious diseases cause millions of deaths each year. The top single disease killers include tuberculosis and diarrheal diseases. The diarrheal diseases caused by cholera toxin and E. coli heat-labile enterotoxin constitute a large part of the diarrhea-related deaths worldwide each year. While there are some efficacious drugs against Vibrio cholerae in the market, their resistance is developing quickly. We wish to develop synthetic molecules that could bind to CT with a high affinity to block the enzymatic reaction catalyzed by CT. We designed, synthesized and evaluated bisubstrate analogs targeting the active site of CT. The most potent inhibitor demonstrated an IC50 of around 40 M. It could serve as a promising drug to treat cholera. The second project is to use -helix mimetics for probing the protein-protein interactions of DosR. The main function of DosR is to mediate the transition of Mycobacteria tuberculosis into dormancy and may contribute to latency. Disruption of the dimerization of DosR could keep MTB in an active state, so that the existing drugs could treat them effectively. We employed small molecules and peptides as tools to achieve the goal.

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