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'Hirudin' is a naturally occurring peptide in the salivary glands of medicinal leeches (''Hirudo medicinalis'') that has a blood anticoagulant property. This is fundamental for the leeches’ alimentary habit of hematophagy, since it keeps the blood flowing after the initial phlebotomy performed by the worm on the host’s skin.

Contents

Structure

Biological activity

References

See also

Structure

In 1884, the British physiologist John Berry Haycraft discovered that the leech secreted a powerful anticoagulant, which he named hirudin, though it was not isolated until the 1950s, nor its structure fully determined until 1976. Full length, hirudin is made up of 65 amino acids. These amino acids are organised into a compact N-terminal domain containing three disulfide bonds and a C-terminal domain which is completely disordered, when the protein is un-complexed in solution.^[1][2] Natural hirudin contains a mixture of various isoforms of the protein. However, recombinant techniques can be used to produce homogeneous preparations of hirudin. Refined structure of the Hirudin-Thrombin complex, Rydell TJ, Tulinsky A. ''et al''., , , J. Mol. Biol., 1991

Biological activity

A key event in the final stages of blood coagulation is the convertion of fibrinogen into fibrin by the serine protease enzyme thrombin.^[3] Thrombin is produced from prothrombin, by the action of an enzyme, prothrombinase, in the final states of coagulation. Fibrin is then cross linked by factor XIII to form a blood clot. The principal inhibitor of thrombin in normal blood circulation is antithrombin III. Similar to antithrombin III, the anticoagulatant activity of hirudin is based on its ability to inhibit the pro-coagulant activity of thrombin.
Hirudin is the most potent natural inhibitor of thrombin. Unlike antithrombin III hirudin binds to and inhibits only the activity of thrombin forms with a specific activity on fibrinogen. Therefore, hirudin prevents or dissolves the formation of clots and thrombi (i.e. it has a thrombolytic activity), and has therapeutic value in blood coagulation disorders, in the treatment of skin hematomas and of superficial varicose veins, either as an injectable or a topical application cream. In some aspects, hirudin has advantages over more commonly used anticoagulants and thrombolytics, such as heparin, as it does not interfere with the biological activity of other serum proteins and can also act on complexed thrombin.
It is difficult to extract large amounts of hirudin from natural sources, so a method for producing and purifying this protein using recombinant biotechnology has been developed. This has led to the development and marketing of a number of hirudin based anticoagulant pharmaceutical products such as Refludan® (lepirudin) and Revasc/Iprivask® (Desirudin). Several other direct thrombin inhibitors are derived chemically from hirudin.

References

1. Solution structure of recombinant hirudin and the Lys-47-Glu mutant: a nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing study, Folkers PJM, Clore GM. ''et al''., , , Biochemistry, 1989
2. Conformation of recombinant desulfatohirudin in aqueous solution determined by nuclear magnetic resonance, Haruyama H. and Wuthrich K., , , Biochemistry, 1989
3. Thrombin and antithrombotics, Fenton JW 2nd, Ofosu SA ''et al''., , , Semin Thromb Hemost, 1998

See also

★ Hirudotherapy