The role of branching glycan of human alpha(1)-acid glycoprotein in enantioselective binding to basic drugs as studied by capillary electrophoresis

The role of the branching glycan structure of human alpha(1)-acid glycoprot ein (AGP) in the interaction with basic drugs was investigated in terms of enantioselectivity in binding ability. AGP was separated by concanavalin A lectin affinity chromatography into two subfractions, the unretained AGP (U R-AGP) which has no biantennary glycan chain and the retained AGP (R-AGP) w hich possesses biantennary oligosaccharide chain(s). The unbound concentrat ions of propranolol (PRO) enantiomers and verapamil (VER) enantiomers in UR -AGP solution and R-AGP solution were determined by high-performance fronta l analysis combined with capillary electrophoresis. It was found that (S)-P RO is bound to UR-AGP and R-AGP more strongly than (R)-PRO, whereas the rev erse applies to VER enantiomers, and that such enantioselectivity is common to these proteins. This suggests that the branching type of glycan chains of AGP does not play significant role in the chiral recognition in binding these basic drugs. (C) 1999 Academic Press.