Hirudo medicinalis

Bode, W., Papamokos, E., Musil, D. The high-resolution X-ray crystal structure of the complex formed between subtilisin Carlsberg and eglin c, an elastase inhibitor from the leech Hirudo medicinalis. Eur. J. Biochem. 166 (1987) 673-692... 

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 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... 

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... 

Figure 8 Venomous animals with chemotherapeutic potential, (a) Vampire bat (Desmodus rotundas (http // www.Animalpicturesarchive.com)) (b) medicinal leech [Hirudo medicinalis)-, (c) oriental fire-bellied toad (Bombina orientalis)-, (d) phantasmal poison frog [Epipedobates tricolor), (e) solitary tunicate sea peach Halocynthia aurantium), (f) glia monster (Heloderma suspectum). Photos (b)-(f) by I. Boyd (Creative Commons Attribution ShareAlike License), H. Van (Public domain), L. Ghoul (Creative Commons Attribution ShareAlike License), A. Rode (Creative Commons Attribution ShareAlike License) and Arpingstone (Public domain), respectively. See website for photo credit (a).

Calin 55000 Hirudo medicinalis Inhibits platelet adhesion... 

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... 

Very recently it was shown that the X-ray analysis of eglin c and its complex with subtilisin revealed a similar type of global structural changes induced by the subtilisin binding.29 Obviously SSI has no sequence or structural similarity with eglin c, which is a monomeric protein having 70 amino acid residues produced by the leech Hirudo medicinalis. It will thus be very interesting to compare the structural as well as biochemical characteristics of these two inhibitors. 

Most of the 600 species of leeches are predatory or ectoparasites few of them are used in medicine and veterinary medicine.80,81 In order to paralyze or consume an invertebrate or vertebrate prey, leeches inject various gland constituents from salivary glands into their victims but they are also able to conserve ingested vertebrate blood by antibiotics and may concentrate it. From Hirudo medicinalis and H. verbena, about 40 different salivary gland constituents are known. 

Elliott EJ (1986) Chemosensory stimuli in feeding behavior of the leech Hirudo medicinalis. J Comp Physiol A Neuroethol Sensory Neural Behav Physiol 159 391-401 Kreuter K, Baier B, ABmann C, Steidle JLM (2008) Prey location and prey choice by the freshwater leech Erpobdella octoculata using foraging kairomones. Freshwater Biol 53 1524-1530... 

Matias I, Bisogno T, Melck D, Vandenbulcke F, Verger-Bocquet M, De PetroceUis L, Sergher-aert C, Breton C, Di Marzo V, Salzet M (2001) Evidence for an endocannabinoid system in the central nervous system of the leech Hirudo medicinalis. Brain Res Mol Brain Res 87 145-159... 

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