Pentosan polysulphate: activation of heparin cofactor II or antithrombin III according to molecular weight fractionation.
The relative potency of pentosan polysulphate in activation of heparin cofactor II/thrombin interaction has been compared to heparin and dermatan sulphate and found to be within the same order. A skewed distribution of molecular weight forms was observed upon gel filtration of pentosan polysulphate with an average molecular weight of 4500 daltons. Two peaks of activity were observed in activation of heparin cofactor II. The greatest activity was observed in high molecular weight fractions (5-fold greater than that of average molecular weight) and a concentration-dependent profile indicated a template mechanism of action. A lower peak of activity was observed at average molecular weight and the effect of increasing concentrations of this material on activity indicated a mechanism involving binding to proteinase inhibitor or proteinase alone. Potentiation of antithrombin III/thrombin interaction was observed only in fractions greater than the average molecular weight. Concentration-dependent profiles indicated binding to antithrombin III and thrombin was a requisite of activation. A fraction of low molecular weight showed no property of activation of antithrombin III or heparin cofactor II/thrombin interaction. Three fractions of high, average and low molecular weights tested in clotting assays showed relative potencies corresponding to those observed in the purified systems.
Scully
M F
MF
Ellis
V
V
Kakkar
V V
VV
D000990:Antithrombin III / Q000378:metabolism*; D000991:Antithrombins / Q000378:metabolism*; D001780:Blood Coagulation Tests; D006023:Glycoproteins / Q000378:metabolism*; D015844:Heparin Cofactor II; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010426:Pentosan Sulfuric Polyester / Q000302:isolation & purification / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000991:Antithrombins; D006023:Glycoproteins; D011134:Polysaccharides; D010426:Pentosan Sulfuric Polyester; D015844:Heparin Cofactor II; D000990:Antithrombin III