Abstract: Novel fibrinolytic zinc metalloproteinases exhibiting direct fibrinolytic activity in plasminogen free systems, no detectable plasminogen activation activity in vitro, and no observable systemic toxicity in vivo as exemplified by the absence of hemorrhagic activity, characterized by peptide bond cleavage specificities which are markedly different from those of the heretofore identified metalloproteinases. Several of the enzymes are further characterized by substantially reduced proteolytic activity (as measured by azocaseinolytic activity in vitro) relative to A.c.contortrix fibrolase. The novel fibrinolytic enzymes with reduced proteolytic activity generally exhibit levels of proteolytic activity less than about 70% of that exhibited by a fibrinolytic enzyme having the activity profile of the enzyme as isolated from A.c.contortrix venom.

Abstract: A protease moiety having direct fibrinolytic activity which is useful in thrombolytic therapy is isolated from snake venom and shown to comprise a metalloproteinase having a molecular weight of from 25 to 27 kd and an isoelectric point of about 6.5 to 7.0. The moiety is separated from venom by a series of diverse fractionation steps including molecular sieve, ion-exchange and affinity chromatography.