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Snake venom fibrin(ogen)olytic enzymes
1Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Centre, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA. markland@usc.edu
Summary
Snake venom contains fibrinolytic enzymes that break down blood clots and prevent their formation. These enzymes, including metalloproteinases and serine proteinases, show promise as clinical treatments for thrombosis.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Snake venoms possess fibrin(ogen)olytic proteinases, including metalloproteinases and serine proteinases.
- These enzymes degrade fibrin and fibrinogen, aiding venom spread and preventing clot formation.
- Historically, fibrinolytic enzymes from snake venom have been investigated for clinical applications.
Purpose of the Study:
- To review the two distinct classes of fibrin(ogen)olytic enzymes found in snake venom.
- To summarize characterization studies of these purified enzymes and their derivatives.
- To discuss the development of a recombinant fibrinolytic enzyme for clinical use.
Main Methods:
- Literature review of identified and characterized fibrin(ogen)olytic enzymes from snake venoms.
- Detailed description of representative enzymes: fibrolase (metalloproteinase) and a serine beta-fibrinogenolytic proteinase.
- Case study on the development of alfimeprase, a recombinant derivative of fibrolase.
Main Results:
- Two classes of fibrin(ogen)olytic enzymes (metalloproteinases and serine proteinases) exist, differing in mechanism and target sequences but serving the same function.
- These enzymes effectively break down fibrin clots and inhibit fibrinogen.
- Alfimeprase, derived from fibrolase, has progressed through Phase II clinical trials as a potential therapeutic agent.
Conclusions:
- Fibrin(ogen)olytic snake venom enzymes represent a promising class of agents for treating occlusive thrombi.
- The distinct properties of metalloproteinases and serine proteinases offer varied therapeutic potential.
- The successful clinical trial progression of alfimeprase validates the therapeutic potential of these venom-derived enzymes.