Kuroda Y, Shibukawa A, Nakagawa T
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
Anal Biochem. 1999 Mar 1;268(1):9-14. doi: 10.1006/abio.1998.3050.
The role of the branching glycan structure of human alpha1-acid glycoprotein (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 (UR-AGP) which has no biantennary glycan chain and the retained AGP (R-AGP) which possesses biantennary oligosaccharide chain(s). The unbound concentrations of propranolol (PRO) enantiomers and verapamil (VER) enantiomers in UR-AGP solution and R-AGP solution were determined by high-performance frontal analysis combined with capillary electrophoresis. It was found that (S)-PRO is bound to UR-AGP and R-AGP more strongly than (R)-PRO, whereas the reverse 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.
从结合能力的对映选择性方面研究了人α1-酸性糖蛋白（AGP）的分支聚糖结构在与碱性药物相互作用中的作用。通过伴刀豆球蛋白A凝集素亲和色谱法将AGP分离为两个亚组分，即没有双天线聚糖链的未保留AGP（UR-AGP）和具有双天线寡糖链的保留AGP（R-AGP）。采用高效前沿分析结合毛细管电泳法测定UR-AGP溶液和R-AGP溶液中普萘洛尔（PRO）对映体和维拉帕米（VER）对映体的未结合浓度。结果发现，（S）-PRO与UR-AGP和R-AGP的结合比（R）-PRO更强，而VER对映体则相反，并且这种对映选择性在这些蛋白质中是常见的。这表明AGP聚糖链的分支类型在结合这些碱性药物的手性识别中不起重要作用。
