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Targeting S100 Calcium-Binding Proteins with Small Molecule Inhibitors

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Calcium-Binding Proteins of the EF-Hand Superfamily

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1929))

Abstract

S100B is a small, dimeric, calcium-binding protein that is implicated in various diseases, most significantly cancer; therefore, there is interest in identifying S100B inhibitors that may have therapeutic value (Bresnick et al. Nat Rev Cancer 15:96–109, 2015; Chong et al. Curr Med Chem 23:1571–1596). Two fluorescence polarization competition assays (FPCA) are described here for S100B and S100A1 that are amenable to high-throughput screening (HTS) campaigns and can be used to determine the binding affinity (K i) of the inhibitors. One FPCA is used to identify and characterize inhibitors of S100B with the aim of finding new therapeutics, and the other was developed as a counter-screen to avoid inhibitors of S100A1 due to its role in regulating skeletal and cardiac muscle function. Also outlined are methods for expressing and purifying S100B and S100A1 in quantities needed for performing large HTS campaigns.

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References

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Authors and Affiliations

  1. Center for Biomolecular Therapeutics (CBT), Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA

    Paul T. Wilder, Kristen M. Varney & David J. Weber

  2. University of Maryland Marlene and Stewart Greenebaum Comprehesive Cancer Center, Baltimore, MD, USA

    Paul T. Wilder, Kristen M. Varney & David J. Weber

Authors
  1. Paul T. Wilder
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  2. Kristen M. Varney
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  3. David J. Weber
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Corresponding author

Correspondence to David J. Weber .

Editor information

Editors and Affiliations

  1. Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University of Zürich, Zürich, Switzerland

    Claus W. Heizmann

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Wilder, P.T., Varney, K.M., Weber, D.J. (2019). Targeting S100 Calcium-Binding Proteins with Small Molecule Inhibitors. In: Heizmann, C. (eds) Calcium-Binding Proteins of the EF-Hand Superfamily. Methods in Molecular Biology, vol 1929. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9030-6_19

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  • DOI: https://doi.org/10.1007/978-1-4939-9030-6_19

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9029-0

  • Online ISBN: 978-1-4939-9030-6

  • eBook Packages: Springer Protocols

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