Wildt William de, Kooijman Huub, Funke Carel, Üstün Bülent, Leika Afranina, Lunenburg Maarten, Kaspersen Frans, Kellenbach Edwin
DTS Aspen Oss B.V., 5223BB Oss, The Netherlands.
Bijvoet Center for Biomolecular Research, Crystal and Structural Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Molecules. 2017 Aug 17;22(8):1362. doi: 10.3390/molecules22081362.
Fondaparinux sodium is a synthetic pentasaccharide representing the high affinity antithrombin III binding site in heparin. It is the active pharmaceutical ingredient of the anticoagulant drug Arixtra. The single crystal X-ray structure of Fondaparinux sodium is reported, unequivocally confirming both structure and absolute configuration. The iduronic acid adopts a somewhat distorted chair conformation. Due to the presence of many sulfur atoms in the highly sulfated pentasaccharide, anomalous dispersion could be applied to determine the absolute configuration. A comparison with the conformation of Fondaparinux in solution, as well as complexed with proteins is presented. The content of the solution reference standard was determined by quantitative NMR using an internal standard both in 1999 and in 2016. A comparison of the results allows the conclusion that this method shows remarkable precision over time, instrumentation and analysts.
磺达肝癸钠是一种合成五糖，代表肝素中高亲和力抗凝血酶III结合位点。它是抗凝血药物磺达肝癸钠的活性药物成分。报道了磺达肝癸钠的单晶X射线结构，明确证实了其结构和绝对构型。艾杜糖醛酸采用了略有扭曲的椅式构象。由于高度硫酸化的五糖中存在许多硫原子，可应用反常散射来确定绝对构型。文中还给出了磺达肝癸钠在溶液中以及与蛋白质复合时的构象比较。1999年和2016年均使用内标通过定量核磁共振法测定了溶液参考标准品的含量。结果比较得出结论，该方法在时间、仪器和分析人员方面均显示出显著的精密度。
