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  • Title: Fibrinolysis with acyl-enzymes: a new approach to thrombolytic therapy.
    Author: Smith RA, Dupe RJ, English PD, Green J.
    Journal: Nature; 1981 Apr 09; 290(5806):505-8. PubMed ID: 7219537.
    Abstract:
    Deep vein thrombosis in man presents a considerable clinical challenge. Despite the availability of prophylactic measures, therapeutic thrombolysis is often necessary, but is difficult and hazardous. Treatments have included the administration of plasmin, other less specific proteolytic enzymes, the indirect plasminogen activator, streptokinase, and the direct activators, urokinase and streptokinase-human plasmin complex. All these treatments have been associated with some haemostatic breakdown, which has discouraged their widespread application. The enzyme components of the coagulation and fibrinolytic pathways can, in general, be classed as serine proteases, with a catalytic mechanism which operates via acyl-enzyme intermediates. Chase and Shaw showed that p-nitrophenyl-p'-guanidinobenzoate could specifically acylate the active centre of trypsin-like enzymes, giving rise to a stable p-guanidinobenzoyl enzyme and other stable acyl-enzymes have since been described. We report here the fibrinolytic use of acylated derivatives of plasmin (E.C.3.4.21.7) and streptokinase-plasmin(ogen) complexes.
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