Langeslay, Derek J.; Young, Robert P.; Beni, Szabolcs; Beecher, Consuelo N.; Mueller, Leonard J.; Larive, Cynthia K.
Sulfamate proton solvent exchange in heparin oligosaccharides: Evidence for a persistent hydrogen bond in the antithrombin-binding pentasaccharide Arixtra
GLYCOBIOLOGY, 22:1173-1182, SEP 2012

Sulfa mate groups (NHSO3-) are important structural elemenls in the glycosaminoglycans (GAGs) heparin and hepa ran 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.

DOI:10.1093/glycob/cws085

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