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Related Experiment Videos

Alpha-fibrinogenases.

S Swenson1, C F Toombs, L Pena

  • 1Department of Biochemistry and Molecular Biology and Norris Comprehensive Cancer Center, Keck School of Medicine University of Southern California, 1303 N. Mission Road, Los Angeles, CA 90033, USA.

Current Drug Targets. Cardiovascular & Haematological Disorders
|December 8, 2004
PubMed
Summary
This summary is machine-generated.

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Snake venom enzymes called alpha-fibrinogenases show promise for treating blood clots. Modified versions like fibrolase and alfimeprase are being developed for clinical use in dissolving thrombi.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Toxicology

Background:

  • Snake venoms contain fibrinolytic metalloproteinases with potential therapeutic applications for occlusive thrombi.
  • Extensive research has identified and characterized fibrinolytic enzymes from various snake species.

Purpose of the Study:

  • To describe the biological properties and clinical potential of alpha-fibrinogenases, a class of fibrinolytic metalloproteinases.
  • To characterize fibrolase, a representative alpha-fibrinogenase from Agkistrodon contortrix contortrix venom.

Main Methods:

  • Biochemical and physiochemical characterization of fibrolase.
  • In vivo activity assessment of fibrolase and its modified forms.
  • In vitro studies using a platelet-avid chimera of fibrolase coupled to an Arg-Gly-Asp (RGD) like peptide.

Related Experiment Videos

  • Modification of fibrolase with polyethylene glycol to reduce circulation clearance rate.
  • Description of alfimeprase, a recombinant fibrinolytic enzyme derived from fibrolase.

    • Main Results:

    • Fibrolase exhibits significant fibrinolytic activity.
    • A fibrolase chimera demonstrated inhibited platelet aggregation and thrombus formation while retaining fibrinolytic function.
    • Polyethylene glycol modification reduced fibrolase clearance.
    • Alfimeprase, a recombinant derivative, is progressing in clinical trials for peripheral arterial occlusions and occluded vascular access catheters.

    Conclusions:

    • Alpha-fibrinogenases, exemplified by fibrolase, possess valuable fibrinolytic properties for treating occlusive thrombi.
    • Engineered variants like alfimeprase show significant clinical potential as thrombolytic agents.
    • Further development of these snake venom-derived enzymes could lead to novel therapeutic strategies for thrombotic disorders.