Investigation of chiral recognition mechanism on chicken alpha(1)-acid glycoprotein using separation system.
Chicken alpha1-acid glycoprotein (alpha1-AGP) consists of 183 amino acid residues and has only one Trp residue at the 26 position. In this study, the Trp26 residue was modified with 2-nitrophenylsulfenyl chloride and chiral separation of neutral, acidic and basic compounds was examined on chicken alpha1-AGP and Trp-modified chicken alpha1-AGP columns. Chiral separation of propranolol, alprenolol and oxprenolol was lost on the Trp-modified chicken alpha1-AGP column, while chlorpheniramine, ketoprofen and benzoin were still enantioseparated on the Trp-modified chicken alpha1-AGP column despite of lower enantioselectivity than that on the chicken alpha1-AGP column. These results suggest that the Trp26 residue could be responsible for chiral recognition of these compounds. Competition studies using N,N-dimethyl-n-octylamine (DMOA) as a competitor indicated that propranolol, alprenolol and oxprenolol competed with DMOA on a single binding site near the Trp26 region and that further bindings of chlorpheniramine, ketoprofen and benzoin occurred at the secondary binding site in a non-competitive fashion with DMOA.
Matsunaga
Hisami
H
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, 11-68, Nishinomiya, Hyogo 663-8179, Japan.
Haginaka
Jun
J
D000818:Animals; D002645:Chickens; D002942:Circular Dichroism; D019075:Electrophoresis, Capillary / Q000379:methods; D009961:Orosomucoid / Q000737:chemistry* / Q000302:isolation & purification
D009961:Orosomucoid