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New, non-quinone fluorogeldanamycin derivatives strongly inhibit Hsp90

Jekaterina Hermane1, Ilona Bułyszko, Simone Eichner

  • 1Institute of Organic Chemistry, Center of Biomolecular Drug Research (BMWZ), Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover (Germany).

Chembiochem : a European Journal of Chemical Biology
|January 10, 2015
PubMed

Keywords:
Hsp90fluorinated compoundsgeldanamycininhibitorsmutasynthesissingle molecule force spectroscopy

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Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These...
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