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J Biotechnol. 2014 Jun 20;180:1-9. doi: 10.1016/j.jbiotec.2014.03.006. Epub 2014 Mar 22.

Microarray-based screening of heat shock protein inhibitors.

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Leibniz Universität Hannover, Institut für Technische Chemie and Biomolekulares Wirkstoffzentrum (BMWZ), Callinstr. 5, D-30167 Hannover, Germany.
Howard Hughes Medical Institute and the Department of Biochemistry & Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158-2517, USA.
Leibniz Universität Hannover, Institut für Organische Chemie and Biomolekulares Wirkstoffzentrum (BMWZ), Schneiderberg 1, D-30167 Hannover, Germany.
Leibniz Universität Hannover, Institut für Biophysik and Biomolekulares Wirkstoffzentrum (BMWZ), Herrenhäuserstr. 2, D-30167 Hannover, Germany. Electronic address:


Based on the importance of heat shock proteins (HSPs) in diseases such as cancer, Alzheimer's disease or malaria, inhibitors of these chaperons are needed. Today's state-of-the-art techniques to identify HSP inhibitors are performed in microplate format, requiring large amounts of proteins and potential inhibitors. In contrast, we have developed a miniaturized protein microarray-based assay to identify novel inhibitors, allowing analysis with 300 pmol of protein. The assay is based on competitive binding of fluorescence-labeled ATP and potential inhibitors to the ATP-binding site of HSP. Therefore, the developed microarray enables the parallel analysis of different ATP-binding proteins on a single microarray. We have demonstrated the possibility of multiplexing by immobilizing full-length human HSP90α and HtpG of Helicobacter pylori on microarrays. Fluorescence-labeled ATP was competed by novel geldanamycin/reblastatin derivatives with IC50 values in the range of 0.5 nM to 4 μM and Z(*)-factors between 0.60 and 0.96. Our results demonstrate the potential of a target-oriented multiplexed protein microarray to identify novel inhibitors for different members of the HSP90 family.


Geldanamycin; Heat shock protein; Inhibitor; Protein microarray

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