Interaction of fucoidan with proteases and inhibitors of coagulation and fibrinolysis

The interactions of fucoidan with glutamic plasminogen (Glu-Plg), two-chain tissue plasminogen activator (t-PA), LMwt-urokinase, thrombin, and antithrombin III (AT-III) were investigated using fucoidan-sepharose affinity chromatography. The results showed 1) a high degree of affinity between fucoidan-sepharose and Glu-Plg; LMwt-urokinase and thrombin while t-PA and AT-III did not bind with fucoidan-sepharose. 2) The double reciprocal plot for the LMwt-urokinase activation of Glu-Plg showed that plasminogen activator inhibitor (PAI-I) inhibited this reaction in a noncompetitive manner and that the presence of fucoidan decreased K-m, for this interaction by 50% and increased K-cat by 30-fold. 3)The double reciprocal plot for the t-PA activation of Glu-Plg showed that PAI-1 inhibited this reaction in a competitive manner and that fucoidan in conjunction with 6-aminohexanoic acid (6-AH) increased K-cat, for this interaction by 5-fold without affecting K-m,. 4)Fucoidan enhanced the interaction of thrombin with both AT-III and heparin cofactor II (HC-II) and it was more effective than unfractionated heparin or LMwt-heparin in enhancing the interaction of HC-II with thrombin. (C) 1997 Elsevier Science Ltd.