Medicinal leech, saliva

The saliva of the medicinal leech contains a battery of substances that interfere with the hemostatic mechanisms of the host. One of these compounds is hirudin, a potent anticoagulant, which maintains the fluidity of the ingested blood and is the most potent inhibitor of thrombin. Upon binding to thrombin, the cleavage of fibrinogen and subsequent clot formation are prevented. The potency and specificity of hirudin make it a useful antithrombin-III-independent alternative to heparin for the control of thrombosis. 

Collectively, the direct thrombin inhibitors are prototypically represented by hirudin, the antithrombotic molecule found in the saliva of the medicinal leech (Hirudo medicinalis), This protein is a 65 amino acid molecule that forms a highly stable but noncovalent complex with thrombin (7). With two domains, the NH2-terminal core domain and the COOH-terminal tail, the hirudin molecule inhibits the catalytic site and the anion-binding exosite in a two-step process. The first step is an ionic interaction that leads to a rearrangement of the thrombin-hirudin complex to form a tighter bond that is stoi-chiometrically I I and irreversible. The apolar-binding site may also be involved in hirudin binding. This complex and... 

The polypeptide hirudin from the saliva of the European medicinal leech inhibits clotting of the leech s blood meal by blockade of the active center of thrombin. This action is independent of AT III and thus also occurs in patients with AT III deficiency. Lepirudin and desrudin are yeast-derived recombinant analogues. They can be used in patients with HIT II. 

The saliva of the medicinal leech contains a battery of substances that interfere with the hemostatic mechanisms of the host. One of these compounds is himdin, a potent... 

Whereas heparin acts indirectly via activation of antithrombin, hirudin—a peptide naturally occurring in the saliva of medicinal leeches (e.g., Hirudo medicinalis)—directly inhibits thrombin. However, hirudin has a limited stability and therefore restricted applicability. 

Hirudin is produced by the medicinal leech and may be extracted from its saliva. It is a 65 amino acid peptide. It is now expressed recombinantly in yeast cells and the recombinant product is almost identical to the naturally occurring protein. It acts directly on thrombin, binding to the active site of thrombin, and preventing the enzymatic cleavage of fibrinogen. It will bind both to free thrombin and to thrombin involved in complexes with fibrinogen. It has the advantage that it does not have the same side effect profile as heparin and thus can be used in heparin-intolerant patients. Bivalimdin is low MW (2180) synthetic peptide which mimics hirudin and binds to thrombin at the same site. 

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