Species-dependency in chiral-drug recognition of serum albumin studied by chromatographic methods.
Stereoselective binding of benzodiazepine and coumarin drugs to serum albumin from human and six mammalian species were studied by chiral chromatographic techniques. The applied methods were affinity chromatography on the albumins immobilized on Sepharose 4B, high-performance liquid chromatography (HPLC) separation on columns based on human serum albumin (HSA) and bovine serum albumin (BSA), and chiral HPLC analysis of ultrafiltrates of solutions containing the racemic drug and the native protein. Substantial differences in preferred configurations and conformations were detected among the species. The binding stereoselectivity of the 2,3-benzodiazepine drug, tofisopam, in human, is opposite to that in all other species. In the binding of 1,4-benzodiazepines, dog albumin is very similar to HSA. Highly preferred binding of (S)-phenprocoumon was found with dog albumin.
Fitos
I
I
Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, H-1525, PO Box 17, Budapest, Hungary. fitosi@chemres.hu
Visy
J
J
Simonyi
M
M
D000818:Animals; D001569:Benzodiazepines / Q000737:chemistry*; D002417:Cattle; D002845:Chromatography / Q000379:methods*; D002846:Chromatography, Affinity / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003374:Coumarins / Q000737:chemistry*; D004285:Dogs; D006736:Horses; D006801:Humans; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D012709:Serum Albumin / Q000032:analysis / Q000737:chemistry* / Q000145:classification*; D012710:Serum Albumin, Bovine / Q000032:analysis / Q000737:chemistry / Q000145:classification; D013045:Species Specificity; D013237:Stereoisomerism; D013552:Swine
D003374:Coumarins; D012709:Serum Albumin; D001569:Benzodiazepines; D012710:Serum Albumin, Bovine