Destabilase, the novel epsilon-(gamma-Glu)-Lys isopeptidase with thrombolytic activity
Biochemistry article published in Blood Coagulation & Fibrinolysis (1991)
Abstract
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.
Resumen
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.
Por qué esto importa para la hirudoterapia
This article characterizes destabilase, an epsilon-(gamma-Glu)-Lys isopeptidase from the salivary gland secretion of Hirudo medicinalis that hydrolyzes isopeptide cross-links in stabilized fibrin, leading to fibrin depolymerization. The study reports that destabilase exists in multiple molecular weight forms (50,000, 25,000, and 12,300), is covalently bound to a lipid component (MW 390) that confers hydrophobic properties, inhibits platelet aggregation, protects against proteolysis, and enables intestinal absorption after oral administration in animals. The authors report near-total (80-100%) thrombolysis of preformed thrombus in rats 70-100 hours after intravenous or oral destabilase administration. For ASH, this is directly relevant as it characterizes a leech-derived enzyme with thrombolytic and antithrombotic properties. However, these are animal-model findings with no human clinical data, and the abstract provides limited methodological detail.
Citación
Destabilase, the novel epsilon-(gamma-Glu)-Lys isopeptidase with thrombolytic activity.
Baskova IP, Nikonov GI · Blood coagulation & fibrinolysis, 1991
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Añadido a la biblioteca ASH: May 26, 2026 · Última actualización del sitio: June 18, 2026