title: Sulfamate proton solvent exchange in heparin oligosaccharides: evidence for a persistent hydrogen bond in the antithrombin-binding pentasaccharide Arixtra.
abstract: 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) 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.
authors.affiliation: Department of Chemistry,  University of California-Riverside, Riverside, CA 92521,  USA.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Langeslay
authors.forename: Robert P
authors.initials: RP
authors.lastname: Young
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Beni
authors.forename: Consuelo N
authors.initials: CN
authors.lastname: Beecher
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Mueller
authors.forename: Cynthia K
authors.initials: CK
authors.lastname: Larive
mesh_terms: D000925:Anticoagulants / Q000737:chemistry*; D000990:Antithrombin III / Q000737:chemistry*; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D000077425:Fondaparinux; D006493:Heparin / Q000737:chemistry*; D006497:Heparan Sulfate / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009844:Oligosaccharides / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*; D011485:Protein Binding; D011522:Protons; D012996:Solutions; D013451:Sulfonic Acids / Q000737:chemistry; D013696:Temperature
chemical_list: D000925:Anticoagulants; D000990:Antithrombin III; D000077425:Fondaparinux; D006493:Heparin; D006497:Heparan Sulfate; D009844:Oligosaccharides; D011134:Polysaccharides; D011522:Protons; D012996:Solutions; D013451:Sulfonic Acids; C005741:sulfamic acid