SpringerProtocols: Abstract: Isothermal Titration Calorimetry Characterization of Drug-Binding Energetics to Blood Proteins

Isothermal Titration Calorimetry Characterization of Drug-Binding Energetics to Blood Proteins

By: Gary W. Caldwell², Zhengyin Yan²

Abstract

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Techniques such as calorimetry, spectroscopy, and hydrodynamic methods can be used to investigate the binding energetics of drugs bound to macromolecules. In this chapter, the authors describe the use of isothermal titration calorimetry (ITC) to measure the binding energetics of drugs bound to blood proteins (i.e., human serum albumin [HSA] and α-acid glycoprotein [AGP]). The stoichiometry (n), the association-binding constant (K _a), and the enthalpy (ΔH ⁰) of binding can be rapidly, directly, and precisely measured using ITC. Because the free energy (ΔG ⁰) and the entropy (ΔS ⁰) are readily calculated from K _a and ΔH ⁰, a complete thermodynamic characterization of binding can be acquired in a single experiment.

Affiliation(s): (2) Johnson & Johnson Pharmaceutical Research & Development, LLC, Drug Discovery, Spring House, PA

Book Title: Optimization in Drug Discovery: In Vitro Methods

Series: Methods in Pharmacology and Toxicology | Pub. Date: Aug-11-2004 | Page Range: 123-149 | DOI: 10.1385/1-59259-800-5:123

Subject: Pharmacology/Toxicology

Key Words: Isothermal titration calorimetry - protein binding

References

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