Destabilase, the novel epsilon-(gamma-Glu)-Lys isopeptidase with thrombolytic activity

The salivary gland secretion of the leech Hirudo medicinalis contains the enzyme destabilase which hydrolyses epsilon-(gamma-Glu)-Lys cross-links in stabilized fibrin. Accumulation of Glu residues instead of the original Gln residues leads to spontaneous depolymerization of destabilized fibrin. L-gamma-Glu-p-nitroanilide; L-gamma-Glu-dansylcadaverine and isopeptide epsilon-(gamma-Glu)-Lys are low-molecular-weight substrates of destabilase. Destabilase probably exists in molecular forms of molecular weight 50,000, 25,000 and 12,300. The protein part of destabilase is covalently bound to a lipid component of molecular weight 390, which has little cross-reactivity to 6-keto-prostaglandin F1 alpha antiserum. The lipid component ensures the hydrophobic properties of destabilase, inhibition of platelet aggregation, protection from proteolysis and absorption from the intestine into blood during oral administration to experimental animals. It also ensures the protective antithrombotic effect. Almost total (80-100%) thrombolysis of preformed thrombus in the rat was achieved by destabilase 70-100 h after i.v. injection or oral administration.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

First detailed enzymological characterization of destabilase, a salivary epsilon-(gamma-Glu)-Lys isopeptidase that hydrolyses cross-links in stabilized fibrin, achieving 80-100% thrombolysis of preformed thrombus in rats.

Leech-derived molecules this paper discusses, each with a full profile in the ASH compound registry:

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