Antithrombic properties of insoluble modified polystyrene: Part I

Area of Science:

• Biochemistry
• Polymer Chemistry
• Hematology

Background:

• Thrombin plays a critical role in blood coagulation.
• Developing materials that interact with coagulation factors is important for hemostasis research.
• Antithrombin III is a primary inhibitor of thrombin.

Purpose of the Study:

• To synthesize and characterize chlorosulfonated polystyrenes grafted with arginyl methyl ester.
• To investigate the interaction of these polymers with thrombin and their effect on clotting time.
• To determine if the observed antithrombin activity is dependent on antithrombin III.

Main Methods:

• Synthesis of chlorosulfonated polystyrenes grafted with arginyl methyl ester.
• Elemental analyses for polymer characterization.
• Assays measuring thrombin clotting time in plasma and fibrinogen solutions.
• Determination of thrombin-resin binding affinity and desorption studies at varying ionic strengths.

Main Results:

• The synthesized polymers were successfully characterized.
• Polymers significantly increased thrombin clotting time in plasma and fibrinogen solutions.
• The antithrombin activity was independent of antithrombin III.
• Direct binding between thrombin and the polymer resin was demonstrated with an affinity constant of 2.3 X 10(6) 1/M.
• Thrombin could be desorbed at high ionic strength, regaining normal activity.

Conclusions:

• Chlorosulfonated polystyrenes grafted with arginyl methyl ester exhibit potent antithrombin activity.
• This activity arises from direct interaction and binding with thrombin, not via antithrombin III.
• The polymer-thrombin interaction is reversible and dependent on ionic strength, suggesting potential applications in modulating coagulation.