Enantioselective plasma protein binding of bimoclomol |
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Authors: | Visy Júlia Fitos Ilona Mády György Urge László Krajcsi Péter Simonyi Miklós |
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Institution: | Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary. visyj@chemres.hu |
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Abstract: | The binding of bimoclomol enantiomers to human plasma, its components, as well as to plasma from monkey, dog, rat, and mouse was investigated by ultrafiltration and equilibrium dialysis. The considerably stronger binding of the (-)-(S)-enantiomer found in human plasma is due to the alpha(1)-acid glycoprotein (AAG) component. The binding parameters for AAG (n(R)K(R) = 1.3 x 10(4) M(-1) and n(S)K(S) = 1.0 x 10(5) M(-1)) revealed high enantioselectivity, while the binding to human serum albumin was found to be weak (nK = 5 x 10(3) M(-1)) and not stereoselective. (-)-(S)-Bimoclomol was extensively displaced in the presence of specific marker ligands for the "FIS" subfraction of human AAG. Comparative binding studies indicated considerable differences between plasma of the five species investigated. |
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Keywords: | stereoselectivity diabetic complications orosomucoid glycoprotein subfractions chiral analysis |
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