Identification of a hexasaccharide sequence able to inhibit thrombin and suitable for ‘polymerisation’

• Published in: Carbohydrate research Vol. 317; no. 1; pp. 63 - 84
• Main Authors: Duchaussoy, Philippe, Jaurand, Guy, Driguez, Pierre-A., Lederman, Isidore, Gourvenec, Françoise, Strassel, Jean-M., Sizun, Philippe, Petitou, Maurice, Herbert, Jean-M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 30.04.1999
• Subjects: Antithrombin; Binding Sites; Carbohydrate Conformation; Carbohydrate Sequence; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents - chemistry; Heparin; Heparin - chemistry; Heparin mimetics; Indicators and Reagents; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Oligosaccharides - chemical synthesis; Oligosaccharides - chemistry; Oligosaccharides - pharmacology; Optical Rotation; Polymers; Thrombin; Thrombin - antagonists & inhibitors; Factor Xa; Thrombin; Heparin; Antithrombin; Heparin mimetics
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/S0008-6215(99)00067-1

Three hexasaccharides, having from low to very high affinity for antithrombin, were synthesised from disaccharide building block precursors. One of them, methyl(sodium 2,3-di- O-methyl-4- O-sodium sulfonato-α- l-idopyranosyluronate)-(1→4)-[(2,3,6-tri- O-sodium sulfonato-α- d-glucopyranosyl)-(1→4)-(sodium 2,3-di- O-methyl-α- l-idopyranosyluronate)-(1→4)] 2-2,3,6-tri- O-sodium sulfonato-α- d-glucopyranoside, obtainable from a single disaccharide building block precursor, constitutes a good starting point for obtaining simple oligosaccharidic heparin mimetics able to inhibit the two coagulation factors thrombin and Factor Xa.