Anticoagulant activity of dermatan polysulfates

Area of Science:

• Biochemistry
• Pharmacology
• Marine Biology

Background:

• Dermatan polysulfates (DPS) are glycosaminoglycans with potential biological activities.
• Marine organisms like hagfish and sharks are sources of unique biomolecules.
• Anticoagulant properties are crucial for managing thrombotic disorders.

Purpose of the Study:

• To investigate the anticoagulant activity of DPS isolated from hagfish and shark.
• To determine the structural factors influencing the anticoagulant potency of DPS.
• To elucidate the mechanism of action of DPS on key coagulation factors.

Main Methods:

• Isolation and purification of DPS from hagfish notochord, hagfish skin, and shark skin.
• Chemical sulfation of dermatan sulfate.
• Assay of anticoagulant activity using activated partial thromboplastin time (APTT).
• Enzymatic digestion with chondroitinase-ABC to analyze disaccharide composition.
• Evaluation of inhibition of thrombin and factor Xa by antithrombin II (AT-III) using chromogenic substrates.

Main Results:

• DPS I, II, III, and chemically sulfated dermatan sulfate exhibited considerable anticoagulant activity in the APTT system.
• Anticoagulant activity correlated with total sulfate content and the presence of sulfated L-iduronic acid residues.
• Molecular weight below 10,000 appeared to reduce anticoagulant activity.
• DPS demonstrated significant inhibition of thrombin inactivation by AT-III, but minimal effect on factor Xa inactivation by AT-III.

Conclusions:

• Dermatan polysulfates from marine sources possess potent anticoagulant properties.
• The anticoagulant efficacy of DPS is dependent on specific structural features, including sulfation patterns and molecular weight.
• DPS primarily exerts its anticoagulant effect by potentiating the inhibition of thrombin by AT-III.