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Molecules 2017, 22(8), 1362; doi:10.3390/molecules22081362

Extended Physicochemical Characterization of the Synthetic Anticoagulant Pentasaccharide Fondaparinux Sodium by Quantitative NMR and Single Crystal X-ray Analysis

1
DTS Aspen Oss B.V., 5223BB Oss, The Netherlands
2
Bijvoet Center for Biomolecular Research, Crystal and Structural Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Received: 31 May 2017 / Revised: 11 August 2017 / Accepted: 14 August 2017 / Published: 17 August 2017
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Abstract

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. View Full-Text
Keywords: Fondaparinux sodium; extended physicochemical characterization; qNMR; single crystal X-ray structure; reference standard; iduronic acid conformation; Arixtra® Fondaparinux sodium; extended physicochemical characterization; qNMR; single crystal X-ray structure; reference standard; iduronic acid conformation; Arixtra®
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Wildt, W.; Kooijman, H.; Funke, C.; Üstün, B.; Leika, A.; Lunenburg, M.; Kaspersen, F.; Kellenbach, E. Extended Physicochemical Characterization of the Synthetic Anticoagulant Pentasaccharide Fondaparinux Sodium by Quantitative NMR and Single Crystal X-ray Analysis. Molecules 2017, 22, 1362.

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