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Enantioselective plasma protein binding of bimoclomol
Author(s) -
Visy Júlia,
Fitos Ilona,
Mády György,
Ürge László,
Krajcsi Péter,
Simonyi Miklós
Publication year - 2002
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.10117
Subject(s) - chemistry , enantiomer , ultrafiltration (renal) , human plasma , plasma protein binding , human serum albumin , glycoprotein , albumin , enantioselective synthesis , orosomucoid , serum albumin , blood proteins , binding site , stereoselectivity , blood plasma , stereochemistry , biochemistry , chromatography , catalysis
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 × 10 4 M −1 and n S K S = 1.0 × 10 5 M −1 ) revealed high enantioselectivity, while the binding to human serum albumin was found to be weak (nK = 5 × 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. Chirality 14:638–642, 2002. © 2002 Wiley‐Liss, Inc.