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

Derek J Langeslay, Robert P Young, Szabolcs Beni, Consuelo N Beecher, Leonard J Mueller, Cynthia K Larive
2012 Glycobiology  
Sulfamate groups (NHSO 3 − ) 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)
more » ... ccharide 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 pmid:22593556 fatcat:ykenygaqovctbcon53lwrkeikm