Enantioselective plasma protein binding of bimoclomol.
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.
Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary. visyj@chemres.hu
Júlia
J
Visy
Ilona
I
Fitos
György
G
Mády
László
L
Urge
Péter
P
Krajcsi
Miklós
M
Simonyi
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D007094:Imides / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009961:Orosomucoid / Q000378:metabolism; D011485:Protein Binding; D011725:Pyridines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D013045:Species Specificity; D013237:Stereoisomerism
D001798:Blood Proteins; D007094:Imides; D009961:Orosomucoid; D011725:Pyridines; D012709:Serum Albumin; C108730:bimoclomol