Linhardt R J, al-Hakim A, Liu S Y, Kim Y S, Fareed J
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242.
Semin Thromb Hemost. 1991;17 Suppl 1:15-22.
A method for characterization and molecular profiling of acidic polysaccharides (such as dermatan sulfates) has been developed. A variety of dermatan sulfates, fractionated dermatan sulfates and low molecular weight dermatan sulfates, were examined. First, bacterial lyase-type enzymes (chondroitinase ABC) were used to depolymerize the polysaccharides. Then, mapping of these oligosaccharides (comparable to peptide mapping of proteins) was performed using gradient PAGE and SAX-HPLC. Bands and peaks observed in these maps were identified using oligosaccharide standards of defined chemical structures and physical properties. The resulting map can be used to point to structural differences among these dermatan sulfates regarding their size, charge, degree of sulfation, and contamination. Fine details of fragmentation patterns and absence or presence of contaminants were detected by silver staining of gels. These differences, particularly the content of----4)alpha-IdoA(1----3)- beta-D-GalNAc4S6S(1----sequences (detected using SAX-HPLC as delta UA(1----3)-beta-D-GalNAc4S6S) may play an important role influencing the activity of dermatan sulfates to potentiate HC II inhibition of Factor IIa.
已开发出一种用于酸性多糖(如硫酸皮肤素)表征和分子谱分析的方法。对多种硫酸皮肤素、分级分离的硫酸皮肤素和低分子量硫酸皮肤素进行了检测。首先,使用细菌裂解酶类(软骨素酶ABC)使多糖解聚。然后,使用梯度PAGE和SAX-HPLC对这些寡糖进行图谱分析(类似于蛋白质的肽图谱分析)。利用具有确定化学结构和物理性质的寡糖标准品鉴定这些图谱中观察到的条带和峰。所得图谱可用于指出这些硫酸皮肤素在大小、电荷、硫酸化程度和污染方面的结构差异。通过凝胶银染检测片段化模式的细微细节以及污染物的有无。这些差异,特别是----4)α-艾杜糖醛酸(1----3)-β-D-半乳糖胺4S6S(1----序列(使用SAX-HPLC检测为δUA(1----3)-β-D-半乳糖胺4S6S)的含量,可能在影响硫酸皮肤素增强HC II对因子IIa抑制作用的活性方面发挥重要作用。