Kishino S, Nomura A, Saitoh M, Sugawara M, Iseki K, Kitabatake A, Miyazaki K
Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Kitaku, Sapporo, Japan.
J Chromatogr B Biomed Sci Appl. 1997 Dec 5;703(1-2):1-6. doi: 10.1016/s0378-4347(97)00403-9.
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.
开发了一种在梯度洗脱程序下使用羟基磷灰石柱对人血清α1-酸性糖蛋白（AAG）糖型进行单步分离的方法。通过脉冲安培检测法测定了六种AAG糖型的N-乙酰神经氨酸和单糖（岩藻糖、N-乙酰葡糖胺、半乳糖和甘露糖）的浓度。对于每种AAG糖型，仅在AAG糖型2和6中观察到了与性别相关的碳水化合物含量显著差异，而非每种AAG糖型都有此差异。研究了聚糖链分支程度与对丙吡胺结合能力之间的关系。与男性糖型相比，女性AAG含有高度唾液酸化的AAG糖型。相反，男性AAG富含低唾液酸化的AAG糖型。此外，发现药物结合能力随聚糖链分支增加而降低。这表明AAG的结合位点受到相对较大的碳水化合物部分（如四天线结构）的阻碍。
