Sulfamate proton solvent exchange in heparin oligosaccharides: Evidence for a persistent hydrogen bond in the antithrombin-binding pentasaccharide Arixtra

Langeslay, D. J. and Young, R. P. and Béni, Szabolcs and Beecher, C. N. and Mueller, L. J. (2012) Sulfamate proton solvent exchange in heparin oligosaccharides: Evidence for a persistent hydrogen bond in the antithrombin-binding pentasaccharide Arixtra. GLYCOBIOLOGY, 22 (9). pp. 1173-1182. ISSN 0959-6658

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Abstract

Sulfamate groups (NHSO3 -) are important structural elements in the glycosaminoglycans (GAGs) heparin and heparan sulfate (HS). In this work, proton nuclear magnetic resonance (NMR) line-shape analysis is used to explore the solvent exchange properties of the sulfamate NH groups within heparin-related mono-, di-, tetra-and pentasaccharides as a function of pH and temperature. The results of these experiments identified a persistent hydrogen bond within the Arixtra (fondaparinux sodium) pentasaccharide between the internal glucosamine sulfamate NH and the adjacent 3-O-sulfo group. This discovery provides new insights into the solution structure of the Arixtra pentasaccharide and suggests that 3-O-sulfation of the heparin N-sulfoglucosamine (GlcNS) residues pre-organize the secondary structure in a way that facilitates binding to antithrombin-III. NMR studies of the GlcNS NH groups can provide important information about heparin structure complementary to that available from NMR spectral analysis of the carbon-bound protons. © 2012 The Author.

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