Hirudo medicinalis Hirudin

The prototype of this class is hirudin, which was originally isolated from the salivary glands of the medicinal leech, Hirudo medicinalis. Hirudin itself is not commercially available, but recombinant technology has permitted production of hirudin derivatives, namely lepirudin and desirudin.29,38,41 Lepirudin has a short half-life of approximately 40 minutes after IV administration and 120 minutes when given SC. Elimination of lepirudin is primarily renal therefore, doses must be adjusted based on the patient s renal function. The dose should be monitored and adjusted to achieve an aPTT ratio of 1.5 to 2.5 times the baseline measurement. Lepirudin is currently approved for use in patients with HIT and related thrombosis. Up to 40% of patients treated with lepirudin will develop antibodies to the drug.29,38,41... 

C28/ c22 ( 39j single-stranded, 65-peptide isolated from the salivary glands of the leech Hirudo medicinalis. Hirudin is the most potent natural inhibitor of the protease thrombin. It is the most eSicient member of the thrombin inhibitors (Ki = 20 fM). Himdin is a very effective anticoagulant, as thrombin acts mainly on... 

Hirudin is a polypeptide derived from the saliva of the leech Hirudo medicinalis that binds to the blood serine proteinase, thrombins, and thus blocks clot formation. 

The most potent thrombin inhibitor is hirudin, originally isolated from the salivary glands of the medicinal leech Hirudo medicinalis. Its inhibition constant is in the femtomolar (10-15 M) range (57). It is a 65-amino-acid tyrosine-sulfated single-chain polypeptide. Recombinant hirudin differs from native hirudin by the absence of the sulfate group on tyrosine 63 (Tyr-63) and is referred to as desulfato hirudin. The loss of this sulfate group reduces the thrombin inhibitory potency by 10-fold. 

The presence of an anticoagulant in the saliva of the leech, Hirudo medicinalis, was first described in 1884. However, it was not until 1957 that the major anticoagulant activity present was purified and named hirudin. Hirudin is a short (65 amino acid) polypeptide, of molecular mass 7000 Da. The tyrosine residue at position 63 is unusual in that it contains a sulfate group. The molecule appears to have two domains. The globular N-terminal domain is stabilized by three disulfide linkages, whereas the C-terminal domain is more elongated and exhibits a high content of acidic amino acids. 

Hirudin 7 000 Hirudo medicinalis Binds to and inhibits thrombin... 

The oleosin fusion procedure was used for the purification of the commercially valuable plant-based blood anticoagulant hirudin in transgenic Brassica carinata and Brassica napus. Hirudin, a natural protein from the medicinal leech Hirudo medicinalis, is superior to other anticoagulants such as heparin. Recombinant hirudin was cleaved from oil-bodies using endoproteinase Factor Xa. Released hirudin was biologically active, as determined by a colorimetric thrombin inhibition assay. 

Hirudin, l-L-lencine-2-L-threonine-63-desnlfo-(Hirudo medicinalis HVl) [CAS]... 

Hirudin [8001-27-2] is a polypeptide of 66 amino acids found in the salivary gland secretions of the leech Hirudo medicinalis (45). It is a potent inhibitor of thrombin and binds to y-thrombin with a dissociation constant of 0.8 x 10 10 M to 2.0 x 10 14 M. Hirudin forms a stable noncovalent complex with free and bound thrombin completely independent of AT-III. This material has now been cloned and expressed in yeast cells (46,47). Its antigenic potential in humans remains to be established. 

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... 

Surgeons have used medicinal leeches Hirudo medicinalis) for years to prevent thrombosis in fine vessels of reattached digits. Hirudin is the potent, specific thrombin inhibitor isolated from the leech. Lepirudin is a rDNA-derived (recombinant yeast) polypeptide that differs from the natural polypeptide, having a terminal leucine instead of isoleucine and missing the sulfate group at Tyr 63 (115). 

Specific products from transgenic plants include enkephalins, IFN-a, human serum albumin, glucocerebrosidase, granulocyte macrophage colony-stimulating factor, tti-antit-rypsin inhibitor (for the treatment of CF, liver diseases, hemorrhages) and hirudin (an anticoagulant for the treatment of thrombosis) from the leech Hirudo medicinalis ... 

Hirudin (lepirudin). Protein from the head and gullet rings of the medicinal leech (Hirudo medicinalis) (ca. 3 mg/leech). H is a heparinoid that delays blood coagulation (thrombin inhibitor). The Mr of H. is ca. 9060 (other reports 10800), it has a high content of acidic amino acid residues. H. is a colorless powder, soluble in water, insoluble in ethanol. The anticoagu-lati ve activity of H. is based on the formation of a compound with Aromhin, so that the latter cannot exert its catalytic effect Commercially available for use in the treatment of thrombosis, hematomas, etc. In Europe, recombinant H. (Refludan ) is marketed for heparin-associated thrombocytopenia. 

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. 

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