Clotting is a remarkable property of blood. Certain substances promote coagulation (procoagulants) and others inhibit coagulation (anticoagulants). Clotting depends on the balance between procoagulants and anticoagulants in the blood. While the anticoagulants normally predominate, the procoagulants get activated and cause clotting when a blood vessel ruptures. Injury to a blood vessel causes a complex cascade of reactions leading to the formation of a clot. The control of clotting is a major medical concern. Heparin, the most frequently used natural anticoagulant, is administered before and after surgery to retard clot formation.
The prevention of clotting is also a concern of blood-sucking organisms, such as leeches which have been used (and misused) in the medical profession for centuries. The active agent responsible for the anticoagulative effect is a protein called hirudin secreted from the salivary glands of Hiduro Medicinalis.
Hirudin is a small, highly active protein with a molecular weight of 7000 Daltons. It specifically binds to thrombin, the enzyme that catalysis the final step of clotting. It forms a stable 1:1 non-covalent complex with thrombin thereby inactivating it and preventing clot formation. Consequently, leech bite, though a minor wound bleeds quiet freely. It is the most potent thrombin inhibitor known because of exceedingly low dissociation constant of hirudin-thrombin complex. The x-ray structure of the complex of hirudin with human thrombin has revealed that numerous interactions are responsible for hirudin’s tight binding to thrombin.
Hirudin is of great medical interest, not only because of its high specificity for thrombin, but because it possesses a number of characteristics which make it superior to the currently used blood anticoagulants such as heparin.
