American Society of Hirudotherapy

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

Biochemistry article published in Blood Coagulation & Fibrinolysis (1991)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Preclinical (animal)Salivary PharmacologyDrug DevelopmentBaskova IP, Nikonov GI · 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.

Publication typeJournal Article
Indexed MeSH termsAnimalsEndopeptidasesFibrinFibrinolytic AgentsKineticsLeechesProtein DenaturationRatsSalivary Proteins and PeptidesThrombolytic TherapyThrombosis

Summary

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.

Why This Matters for Hirudotherapy

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.

Citation

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

Baskova IP, Nikonov GI · Blood coagulation & fibrinolysis, 1991

DOI

Added to ASH library: May 26, 2026 · Site last updated: June 18, 2026

This website provides educational information and does not constitute medical advice, diagnosis, or treatment recommendations. Medicinal leech therapy carries clinically meaningful risks and should be performed only by qualified clinicians under institutionally approved protocols. FDA 510(k) clearance for medicinal leeches is limited to specific indications; investigational and off-label discussions are labeled accordingly. For patient-specific guidance, consult a qualified healthcare provider.