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Inhibitor Binding to Carbonic Anhydrases by Isothermal Titration Calorimetry

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Carbonic Anhydrase as Drug Target

Abstract

Small-molecule drug-candidate compounds are ranked by their capability, primarily described as affinity, to bind a target protein, for example, human carbonic anhydrase (CA), a subject of this book. One of the methods of choice to determine the affinity is isothermal titration calorimetry (ITC), a biophysical technique that enables the determination of the thermodynamic parameters of binding between a protein and a small molecule, both unmodified and free in solution—the change in Gibbs energy, enthalpy, entropy, and heat capacity—through the direct measurement of the heat exchange upon binding. ITC is the only technique that directly determines the change in enthalpy upon binding at isothermal and isobaric conditions providing additional information on the mechanism of interaction and thus plays an important role in drug design. In this chapter we describe the main principles, advantages, and disadvantages of the ITC technique, as well as its use to determine the enthalpy change upon sulfonamide inhibitor binding to catalytically active CA isoforms.

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Acknowledgements

D. M. thanks the Research Council of Lithuania (project TAP LLT-1/2016). M. B. thanks Fundação para a Ciência e Tecnologia (FCT-Portugal) (project UID/QUI/0081/2013 and NORTE-01-0145-FEDER-000028 (Sustainable Advanced Materials (SAM), Programa Operacional Regional do Norte (Norte 2020).

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Authors and Affiliations

  1. Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania

    Vaida Paketurytė, Asta Zubrienė & Daumantas Matulis

  2. Department of Chemical and Materials Engineering, National Central University, Taoyuan City, Taiwan

    Wen-Yih Chen

  3. Molecular Biophysics, Technische Universität Kaiserslautern (TUK), Kaiserslautern, Germany

    Sandro Keller

  4. CIQUP, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal

    Margarida Bastos

  5. Biophysical Solutions, Inc., Ambler, PA, USA

    Matthew J. Todd

  6. Department of Molecular and Cell Biology and Astbury Center for Structural Biology, University of Leeds, Leeds, UK

    John E. Ladbury

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  1. Vaida Paketurytė
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Correspondence to Daumantas Matulis .

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  1. Department of Biothermodynamics and Drug Design, Vilnius University, Life Sciences Center, Institute of Biotechnology, Vilnius, Lithuania

    Daumantas Matulis

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Paketurytė, V. et al. (2019). Inhibitor Binding to Carbonic Anhydrases by Isothermal Titration Calorimetry. In: Matulis, D. (eds) Carbonic Anhydrase as Drug Target. Springer, Cham. https://doi.org/10.1007/978-3-030-12780-0_6

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