A novel semi-synthetic sulphated polysaccharide with potent antithrombin activity

Area of Science:

• Biochemistry
• Pharmacology
• Marine Biology

Background:

• Mucopolysaccharides are complex carbohydrates with diverse biological roles.
• Heparin is a well-known anticoagulant, but its mechanism relies on antithrombin III (AT III).
• The search for novel anticoagulants with different mechanisms is ongoing.

Purpose of the Study:

• To isolate and characterize a novel mucopolysaccharide from mussel broth.
• To investigate the anticoagulant and antithrombotic properties of the purified sulphated polysaccharide (S-Lim).
• To compare the mechanism of action of S-Lim with that of heparin.

Main Methods:

• Isolation and sulphation of mucopolysaccharide from mussel broth.
• Electrophoresis and molecular weight determination.
• Anticoagulant assays including thrombin-fibrinogen clotting time, activated partial thromboplastin time (aPTT), and antithrombin III (AT III) cofactor activity.
• Assessment of inhibition of thrombin-induced platelet aggregation and factor XIII activation.

Main Results:

• A homogenous sulphated polysaccharide (S-Lim) with a molecular weight of ~40,000 daltons and 12% sulphur content was obtained.
• S-Lim demonstrated significant anticoagulant activity in human plasma, functioning in both thrombin-fibrinogen and aPTT systems.
• Unlike heparin, S-Lim's anticoagulant effect was independent of AT III.
• S-Lim inhibited thrombin-induced platelet aggregation and factor XIII activation but did not affect factor Xa activity.
• Protamine sulfate effectively inhibited S-Lim's anticoagulant effect.
• The potency of S-Lim was estimated at 40-50 international units (iu) of heparin per milligram.

Conclusions:

• The isolated and sulphated mucopolysaccharide, S-Lim, acts as a potent, pure antithrombin.
• S-Lim's unique mechanism of action, independent of AT III, distinguishes it from heparin and other heparinoids.
• S-Lim exhibits potential as a novel anticoagulant agent with a distinct pharmacological profile.