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Analysis of binding affinity between antiplatelet drug dipyridamole and human serum alpha-1 acid glycoprotein utilizing microscale thermophoresis

An understanding of the interaction of various drugs with plasma proteins is essential for understanding their systemic pharmacology and toxicology. Thus, information concerning the effects of the acute phase responses on the ligand binding ability of plasma can be used to optimize drug administration protocols in clinical practice. Alpha-1 acid glycoprotein (AGP) has been reported to be a major plasma protein that strongly binds basic drugs such as dipyridamole, drug that is easily synthesized from 5-nitroorotic acid (1-2). In this study, microscale thermophoresis (MST) is used as an analytical technique for determining binding affinity between antiplatelet drug dipyridamole and AGP. MST is a powerful technique in quantitation of binding events based on the movement of molecules in microscopic temperature gradient. The concentration of AGP in plasma can significantly increase in various diseases (cancer, inflammatory disease) or following trauma (burns, surgery). Changes in AGP concentration could potentially alter the free fraction of drugs in plasma or at their target sites and eventually affect their pharmacokinetic disposition and pharmacological action. Given that an increase number of drugs have been shown to bind preferentially to AGP, a better understanding of this unique interaction may provide great benefit for drug discovery and development (3). Knowing the change in drug binding affinity to AGP as well as knowing the change in different medical situations can improve the therapeutic and/or toxicological outcome of treatment in dealing with a large number of different drugs.

alpha-acid glycoprotein, plasma protein binding, dipyridamole, binding constant, thermophoresis

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