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Evaluation of thermodynamic parameters between antidepressant imipramine and human alpha1-acid glycoprotein by isothermal titration calorimetry

α1-acid glycoprotein (AGP, also known as orosomucoid) is an important plasma protein involved in the binding and transport of many drugs, especially basic compounds [1]. This research uses a novel sensitive and modern isothermal titration calorimetry (ITC) technique for characterization of microscopic thermodynamic parameters that trigger the binding of drugs to AGP [2]. This assay is a convenient and widely used approach to directly measure the amount of heat released or absorbed during association processes of biomolecules, such as protein-drug, in solution and to quantitatively estimate the interaction affinity. The binding of basic drug imipramine displayed an exothermically driven binding interaction with AGP. The exothermic binding energy of compounds were guided by a combination of favorable (negative) enthalpy (ΔrH = –11.2 kcal/mol) and favorable (positive) entropy (ΔrS = 4.62 kcal/mol K) contribution to the Gibbs free energy (ΔrG = –6.57 kcal/mol) with dissociation constant (KD = 23.7 "μ" M). By accessing the enthalpy change, we get a step closer in estimating the driving forces that characterize the interaction of a protein with a drug, information much needed in the drug discovery process.

alpha-acid glycoprotein ; plasma protein binding ; ITC

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