title: Antithrombin-mediated inhibition of factor VIIa-tissue factor complex by the synthetic pentasaccharide representing the heparin binding site to antithrombin.
abstract: We examined the effect of the synthetic pentasaccharide representing the minimal binding site of heparin to antithrombin on the antithrombin-mediated inactivation of factor VIIa bound to tissue factor. This effect was compared to the effect of unfractionated heparin. Using purified recombinant human coagulation factors and either a clotting or an amidolytic assay for the determination of the residual activity of factor VIIa, we showed that the pentasaccharide was an efficient antithrombin-dependent inhibitor of the coagulant activity of tissue factor-factor VIIa complex. In our experimental conditions, assuming a mean MW of 14,000 for heparin, the molar pseudo-first order rate constants for ATIII-mediated FVIIa inhibition by ATIII-binding heparin and by the synthetic pentasaccharide were found to be similar with respective values of 104,000 +/- 10,500 min-1 and 112,000 +/- 12,000 min-1 (mean +/- s.e.m., n = 3).
authors.affiliation: Haemobiology Research Department, Sanofi Recherche, Toulouse, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Lormeau
authors.forename: J P
authors.initials: JP
authors.lastname: Herault
authors.forename: J M
authors.initials: JM
authors.lastname: Herbert
mesh_terms: D000990:Antithrombin III / Q000378:metabolism*; D001665:Binding Sites; D005167:Factor VII / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015942:Factor VIIa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D009844:Oligosaccharides / Q000494:pharmacology*; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D005343:Fibrinolytic Agents; D009844:Oligosaccharides; C064764:PENTA; D000990:Antithrombin III; D005167:Factor VII; D006493:Heparin; D013925:Thromboplastin; D015942:Factor VIIa