title: Single-step isolation method for six glycoforms of human alpha1-acid glycoprotein by hydroxylapatite chromatography and study of their binding capacities for disopyramide.
abstract: A single-step isolation method for the glycoforms of human serum alpha1-acid glycoprotein (AAG) using a hydroxylapatite column under a gradient elution program was developed. The concentrations of N-acetylneuraminic acid and monosaccharides (fucose, N-acetylglucosamine, galactose and mannose) of six AAG glycoforms were determined by the pulsedamperometric detection method. For each AAG glycoform, significant sex-related differences in carbohydrate content have been observed only for AAG glycoforms two and six, and not for each AAG glycoform. The relationship between the extent of the branch in the glycan chain and the binding capacity to disopyramide were examined. Female AAG contained highly sialylated AAG glycoforms compared to male glycoforms. Conversely, male AAG was rich in the lower sialylated AAG glycoform. Furthermore, it was found that the drug binding capacity decreases with increasing branching of the glycan chain. This suggests that the binding sites of AAG are hindered by a relatively large carbohydrate moiety, such as tetraantennary structures.
authors.affiliation: Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Kitaku, Sapporo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kishino
authors.forename: A
authors.initials: A
authors.lastname: Nomura
authors.forename: M
authors.initials: M
authors.lastname: Saitoh
authors.forename: M
authors.initials: M
authors.lastname: Sugawara
authors.forename: K
authors.initials: K
authors.lastname: Iseki
authors.forename: A
authors.initials: A
authors.lastname: Kitabatake
authors.forename: K
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000328:Adult; D002241:Carbohydrates / Q000032:analysis* / Q000145:classification; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004206:Disopyramide / Q000378:metabolism; D017886:Durapatite / Q000737:chemistry; D005260:Female; D006031:Glycosylation; D006801:Humans; D008297:Male; D009961:Orosomucoid / Q000737:chemistry* / Q000302:isolation & purification* / Q000378:metabolism; D012727:Sex Characteristics; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002241:Carbohydrates; D009961:Orosomucoid; D017886:Durapatite; D004206:Disopyramide