Characterization of the anticoagulant actions of a semisynthetic curdlan sulfate

Sulfation of curdlan, a natural, linear beta-1,3-glucan results in potent a nticoagulant and antithrombotic agents. The different activity characterist ics in the classical coagulation assays were shown to depend on various str uctural parameters. To obtain more detailed information about their structu re-dependent mechanisms of action, one representative of these beta-1,3-glu can sulfates (CurS), was further investigated using several coagulation ass ays and amidolytic tests with chromogenic substrates, The mode of action of CurS differs from that of heparin, CurS reduces the thrombin formation by principally inhibiting the intrinsic FXa generation. As shown by amidolytic assays, it eliminates already generated thrombin mainly by accelerating th e HCII-mediated thrombin inactivation, whereas its AT-mediated anti-thrombi n activity is considerably lower than that of heparin, Further, it prevents the thrombin-mediated fibrin polymerization by directly interfering with t he thrombin action on fibrinogen as well as by binding to fibrinogen. Final ly, CurS is capable to activate the contact system with the consequence of a potential fibrinolytic effect. In conclusion, beta-1,3-glucan sulfates do not inhibit the blood coagulation nonspecifically due to their anionic cha racter: but in dependence on their individual structure, they interfere spe cifically with the coagulation process at several sites. (C) 2000 Elsevier Science Ltd. All rights reserved.