In Vitro Studies on a Proteolytic Enzyme from Aspergillus Oryzae (Protease I)

Abstract

Summary1. Protease I was found to have potent fibrinolytic activity in concentrations which exceeded the blood inhibitory capacity when tested on fibrin plates and artificial thrombi.2. Plasma inhibited the proteolytic activity of protease I to a greater extent than serum; serum had a greater inhibitory effect on protease I than on plasmin. Trasylol did not inhibit the proteolytic action of protease I.3. Protease I caused the slow formation of fibrin in plasma in concentrations which did not produce fibrinogenolysis; this effect was seen in Al(OH)3-adsorbed plasma, and was not inhibited by heparin. Protease I also shortened the recalcified plasma clotting time.4. The fibrinogenolytic action of protease I was more rapid than its fibrinolytic action both in the presence and absence of plasma inhibitors. No concentration of protease I lysed fibrin in plasma without prior destruction or conversion to fibrin of the surrounding plasma fibrinogen.5. It is concluded from these in vitro studies that protease I does not have the properties necessary for a satisfactory thrombolytic agent.

Anticoagulant and Thrombolytic Drugs1 I

“…A proteolytic enzyme (CA-7; Protease I) has been prepared from Aspergillus oryzae, but in vitro studies have indicated that it shares the lack of specificity for fibrin of other proteolytic enzymes (Ogston and Ogston, 1968). It is accordingly unlikely to function as a safe systemic thrombolytic agent, but its local use, for example, to clear Scribner shunts, is not precluded.…”