title: Assessment through chemical synthesis of the size of the heparin sequence involved in thrombin inhibition.
abstract: Deca- to eicosasaccharides having the generic structure methyl(sodium 2,3-di-O-methyl-4-O-sodium sulfonato-alpha-L-idopyranosyluronate)-(1-->4)-[(2,3,6-tri-O-sodiu m sulfonato-alpha-D-glucopyranosyl)-(1-->4)-(sodium 2,3-di-O-methyl-alpha-L-idopyranosyluronate)-(1-->4)]n-2,3,6-tri-O-sodiu m sulfonato-alpha-D-glucopyranoside have been synthesized from a single disaccharide precursor. All of them bind to and activate antithrombin. When n < or = 6 only Factor Xa inhibition is observed, whereas when n > 6 Factor Xa and thrombin are both inhibited in the presence of antithrombin. These results indicate that, in heparin, the sequence involved in antithrombin-catalyzed thrombin inhibition is a pentadeca- or a hexadecasaccharide.
authors.affiliation: Sanofi Recherche, Haemobiology Research Department, Toulouse, France.
authors.forename: P
authors.initials: P
authors.lastname: Duchaussoy
authors.forename: G
authors.initials: G
authors.lastname: Jaurand
authors.forename: P A
authors.initials: PA
authors.lastname: Driguez
authors.forename: I
authors.initials: I
authors.lastname: Lederman
authors.forename: M L
authors.initials: ML
authors.lastname: Ceccato
authors.forename: F
authors.initials: F
authors.lastname: Gourvenec
authors.forename: J M
authors.initials: JM
authors.lastname: Strassel
authors.forename: P
authors.initials: P
authors.lastname: Sizun
authors.forename: M
authors.initials: M
authors.lastname: Petitou
authors.forename: J M
authors.initials: JM
authors.lastname: Herbert
mesh_terms: D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006493:Heparin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009904:Optical Rotation; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D004187:Disaccharides; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D007202:Indicators and Reagents; D009844:Oligosaccharides; D006493:Heparin; D013917:Thrombin