Antithrombin-mediated inhibition of factor VIIa-tissue factor complex by the synthetic pentasaccharide representing the heparin binding site to antithrombin.
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).
Lormeau
J C
JC
Haemobiology Research Department, Sanofi Recherche, Toulouse, France.
Herault
J P
JP
Herbert
J M
JM
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
D005343:Fibrinolytic Agents; D009844:Oligosaccharides; C064764:PENTA; D000990:Antithrombin III; D005167:Factor VII; D006493:Heparin; D013925:Thromboplastin; D015942:Factor VIIa