比莫克隆的对映体选择性血浆蛋白结合

Enantioselective plasma protein binding of bimoclomol.

作者信息

Visy Júlia, Fitos Ilona, Mády György, Urge László, Krajcsi Péter, Simonyi Miklós

机构信息

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

出版信息

Chirality. 2002 Aug;14(8):638-42. doi: 10.1002/chir.10117.

DOI:10.1002/chir.10117

PMID:12125033

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.

摘要

通过超滤和平衡透析研究了比莫克隆醇对映体与人血浆及其成分以及猴、狗、大鼠和小鼠血浆的结合情况。在人血浆中发现的(-)-(S)-对映体结合力明显更强，这是由于α(1)-酸性糖蛋白（AAG）成分所致。AAG的结合参数（n(R)K(R) = 1.3×10⁴ M⁻¹ 和 n(S)K(S) = 1.0×10⁵ M⁻¹）显示出高对映选择性，而与人类血清白蛋白的结合较弱（nK = 5×10³ M⁻¹）且无立体选择性。在存在人类AAG“FIS”亚组分的特异性标记配体时，(-)-(S)-比莫克隆醇被大量置换。比较结合研究表明，所研究的五个物种的血浆之间存在显著差异。