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Revealing the Energetics of Ligand-Quadruplex Interactions Using Isothermal Titration Calorimetry

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G-Quadruplex Nucleic Acids

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2035))

Abstract

The thermodynamic characterization of G4-ligand interactions has shown to be a powerful adjunct to structural information in the rational design and optimization of potent G-quadruplex ligands for use in therapeutics, diagnostics, or other technological applications. Isothermal titration calorimetry (ITC) can resolve energetic contributions to complex formation and constitutes the only available experimental method to directly measure binding enthalpies. A general protocol for using ITC in studies on quadruplex-ligand interactions with details on the experimental setup, data analysis, and potential pitfalls is presented. The methodologies used are illustrated on results obtained from the targeting of a parallel DNA G-quadruplex with a G4-binding indoloquinoline derivative.

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Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (INST 292/138-1).

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Authors and Affiliations

  1. Institute of Biochemistry, University of Greifswald, Greifswald, Germany

    Andrea Funke & Klaus Weisz

Authors
  1. Andrea Funke
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  2. Klaus Weisz
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Corresponding author

Correspondence to Klaus Weisz .

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Editors and Affiliations

  1. Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, Purdue Center for Cancer Research, Purdue Institute for Drug Discovery, West Lafayette, IN, USA

    Danzhou Yang

  2. Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN, USA

    Clement Lin

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Funke, A., Weisz, K. (2019). Revealing the Energetics of Ligand-Quadruplex Interactions Using Isothermal Titration Calorimetry. In: Yang, D., Lin, C. (eds) G-Quadruplex Nucleic Acids. Methods in Molecular Biology, vol 2035. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9666-7_3

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  • DOI: https://doi.org/10.1007/978-1-4939-9666-7_3

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9665-0

  • Online ISBN: 978-1-4939-9666-7

  • eBook Packages: Springer Protocols

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