title: Biantennary glycans as well as genetic variants of alpha1-acid glycoprotein control the enantioselectivity and binding affinity of oxybutynin.
abstract: OBJECTIVE
  The purpose of this study was to investigate the role of biantennary branching glycans of alpha1-acid glycoprotein (AGP) and its genetic variants in the enantioselective binding of oxybutynin (OXY).
  
  
  METHODS
  Human native AGP was separated using imminodiacetate-copper (II) affinity chromatography into two fractions, the A variant and a mixture of the F1 and S variants (F1-S). These fractionated AGPs were further separated by concanavalin A affinity chromatography into two fractions, with and without biantenarry glycans. An on-line high-performance liquid chromatography (HPLC) system consisting of a high-performance frontal analysis column, an extraction column, and an analytical HPLC column was developed to determine the binding affinities of OXY enantiomers for respective AGP species.
  
  
  RESULTS
  The total binding affinity as well as the enantiomeric selectivity of OXY in the F1-S mixed variant was significantly higher than that for the A variant, indicating that the chiral recognition ability of native AGP for the OXY enantiomers highly depends on the F1-S mixed variant. Furthermore, not only the genetic variants but also bianntenary glycans of AGP affect the binding affinity of OXY and are also responsible for the enantioselectivity.
  
  
  CONCLUSIONS
  Both genetic variants and glycan structures significantly contribute to the enantioselectivity and the binding affinity of OXY.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kimura
authors.forename: Akimasa
authors.initials: A
authors.lastname: Shibukawa
authors.forename: Katsumi
authors.initials: K
authors.lastname: Matsuzaki
mesh_terms: D002236:Carbohydrate Conformation; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008333:Mandelic Acids / Q000737:chemistry / Q000378:metabolism*; D018727:Muscarinic Antagonists / Q000378:metabolism*; D009961:Orosomucoid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D009961:Orosomucoid; D011134:Polysaccharides; D020033:Protein Isoforms; C005419:oxybutynin