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.