Enantioselective plasma protein binding of bimoclomol

Authors

  • Júlia Visy,

    Corresponding author
    1. Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary
    • Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Department of Molecular Pharmacology, H-1525 Budapest, P.O.B. 17, Hungary
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  • Ilona Fitos,

    1. Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary
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  • György Mády,

    1. Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary
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  • László Ürge,

    1. Biorex R&D. Co., Veszprém, Hungary
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  • Péter Krajcsi,

    1. Biorex R&D. Co., Veszprém, Hungary
    2. Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary
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  • Miklós Simonyi

    1. Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary
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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 alpha1-acid glycoprotein (AAG) component. The binding parameters for AAG (nRKR = 1.3 × 104 M−1 and nSKS = 1.0 × 105 M−1) revealed high enantioselectivity, while the binding to human serum albumin was found to be weak (nK = 5 × 103 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. Chirality 14:638–642, 2002. © 2002 Wiley-Liss, Inc.

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