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A systematic protocol for the characterization of Hsp90 modulators |
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| Authors: | Matts Robert L Brandt Gary E L Lu Yuanming Dixit Anshuman Mollapour Mehdi Wang Suiquan Donnelly Alison C Neckers Leonard Verkhivker Gennady Blagg Brian S J |
| Institution: | a Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078, United States b Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Malott 4070, Lawrence, KS 66045-7582, United States c The Center for Bioinformatics, The University of Kansas, 1251 Wescoe Hall Drive, Malott 4070, Lawrence, KS 66045-7582, United States d Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Dr., MSC 1107, Bldg 10 CRC, Room 1-5942, Bethesda, MD 20892-1107, United States |
| Abstract: | Several Hsp90 modulators have been identified including the N-terminal ligand geldanamycin (GDA), the C-terminal ligand novobiocin (NB), and the co-chaperone disruptor celastrol. Other Hsp90 modulators elicit a mechanism of action that remains unknown. For example, the natural product gedunin and the synthetic anti-spermatogenic agent H2-gamendazole, recently identified Hsp90 modulators, manifest biological activity through undefined mechanisms. Herein, we report a series of biochemical techniques used to classify such modulators into identifiable categories. Such studies provided evidence that gedunin and H2-gamendazole both modulate Hsp90 via a mechanism similar to celastrol, and unlike NB or GDA. |
| Keywords: | Heat shock protein 90 Novobiocin Geldanamycin Celastrol Gedunin |
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