Recombinant Hirudin, a potent thrombin inhibitor, originates from the medicinal leech. Its action directly targets thrombin, unlike other clotting factors. Hirudin exhibits a distinct mechanism in inhibiting thrombin. The conversion of fibrinogen to fibrin, catalyzed by the serine protease enzyme thrombin, represents a crucial step in the final stages of blood coagulation. During these final stages, prothrombinase converts prothrombin to thrombin, and subsequently, factor XIII cross-links fibrin to form a blood clot. Antithrombin III serves as the primary regulator of thrombin in normal blood circulation. The anticoagulant property of hirudin stems from its ability to inhibit the pro-coagulant function of thrombin, similar to antithrombin III. Notably, hirudin stands out as the most potent naturally occurring thrombin inhibitor. Its specificity lies in binding to and inhibiting only the fibrinogen-acting forms of thrombin, contrasting with antithrombin III. This specific action confers thrombolytic properties to hirudin, as it prevents or dissolves clot and thrombi formation. The therapeutic significance of hirudin extends to blood coagulation disorders, skin hematomas, and superficial varicose veins. Unlike common anticoagulants and thrombolytics, hirudin doesn't interfere with other serum proteins' biological activities and can even act on complexed thrombin. Due to the complexity of extracting large amounts of hirudin from natural sources, recombinant biotechnology has emerged as a viable method for its production and purification.
Hirudin is a potent and specific thrombin inhibitor originally derived from the salivary glands of the medicinal leech, Hirudo medicinalis. It is a small peptide consisting of 64-66 amino acids with a molecular weight of approximately 7000 Da . Hirudin has been used for its anticoagulant properties for centuries, particularly in traditional Chinese medicine.
The anticoagulant properties of leech extracts were first observed in 1884 by Haycraft, and the term “hirudin” was coined by Jacoby in 1904 . In 1955, Markwardt successfully isolated relatively pure hirudin from the salivary glands of Hirudo medicinalis, which significantly advanced the research on thrombin inhibitors . The complete amino acid sequence of hirudin was described by Dodt et al. in 1984 .
Recombinant hirudin is synthesized using bioengineering techniques, resulting in a product with a chemical structure and pharmacological activity similar to natural hirudin . The two recombinant hirudin preparations available on the market are produced in Saccharomyces cerevisiae using recombinant technology . These recombinant forms lack the sulfation of the tyrosine residue at position 63, often referred to as desulfatohirudins .
Hirudin and its recombinant forms have demonstrated potent antithrombotic effects. They inhibit thrombin-mediated conversion of fibrinogen to fibrin, thereby preventing clot formation . Additionally, hirudin derivatives have shown various bioactivities, including wound repair, anti-fibrosis, anti-tumor, and effects on diabetic complications .