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Vol. 31, No. 3-6, 2001
Issue release date: May–December 2001 (March 2002)
Section title: Fibrinolysis
Haemostasis 2001;31:118–122
(DOI:10.1159/000048054)

Vampire Bat Plasminogen Activator DSPA-Alpha-1 (Desmoteplase): A Thrombolytic Drug Optimized by Natural Selection

Schleuning W.-D.
Paion GmbH, Research Center Berlin, Berlin, Germany
email Corresponding Author

Abstract

Plasminogen activators are enzymes found in all vertebrate species investigated so far. Their physiological function is the generation of localized proteolysis in the context of tissue remodeling, wound healing and neuronal plasticity. The common vampire bat (Desmodus rotundus) is a New World species that feeds exclusively on blood. Its saliva contains highly potent plasminogen activators, specialized in rapid lysis of fresh blood clots. Biochemical and pharmacological evidence indicates that these plasminogen activators represent a new class of thrombolytics with pharmacological and toxicological properties superior to human tissue-type plasminogen activator, the clot dissolving agent now most frequently used in medicine. A form of the enzyme produced by recombinant DNA technology is currently employed to test this hypothesis in clinical studies.

© 2002 S. Karger AG, Basel


  

Key Words

  • Plasminogen activator
  • DSPA
  • Desmoteplase
  • Thrombolytic
  • Fibrinolytic
  • Fibrin specificity
  • Stroke

References

  1. Hawkey C: Plasminogen activator in the saliva of the vampire bat Desmodus rotundus. Nature 1966;211:434–435.

    External Resources

  2. Krätzschmar J, Haendler B, Langer G, Boidol W, Bringmann P, Alagon A, Donner P, Schleuning W-D: The plasminogen activator family from the salivary gland of the vampire bat Desmodus rotundus: Cloning and expression. Gene 1991;105:229–237.
  3. Schleuning W-D, Alagon A, Boidol W, Bringmann P, Petri T, Krätzschmar J, Haendler B, Baldus B, Witt W, Donner P: Plasminogen activators from the saliva of Desmodus rotundus (common vampire bat): Unique fibrin specificity. Ann NY Acad Sci 1992;667:395–403.
  4. Petri T, Langer G, Bringmann P, Cashion L, Shallow S, Schleuning W-D: Production of vampire bat plasminogen activator DSPAα1 in CHO and insect cells. J Biotechnol 1995;39:75–83.

    External Resources

  5. Bringmann P, Gruber D, Liese A, Toschi J, Kraetzschmar J, Schleuning W-D, Donner P: Structural features mediating fibrin selectivity of vampire bat plasminogen activators. J Biol Chem 1995;270:25596–25603.
  6. Renatus M, Stubbs MT, Huber R, Bringmann P, Donner P, Schleuning W-D, Bode W: Catalytic domain structure of vampire bat plasminogen activator: A molecular paradigm for proteolysis without activation cleavage. Biochemistry 1997;36:13483–13493.

    External Resources

  7. Kingston IB, Castro MJ, Anderson S: In vitro stimulation of tissue-type plasminogen activator by Alzheimer amyloid beta-peptide analogues. Nat Med 1995;1:138–142.

    External Resources

  8. Wang YF, Tsirka SE, Strickland S, Stieg PE, Soriano SG, Lipton SA: Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nat Med 1998;4:228–231.
  9. Witt W, Baldus B, Bringmann P, Cashion L, Donner P, Schleuning W-D: Thrombolytic properties of Desmodus rotundus (vampire bat) salivary plasminogen activator in experimental pulmonary embolism in rats. Blood 1992;79:1213–1217.
  10. Muschick P, Zeggert D, Donner P, Witt W: Thrombolytic properties of Desmodus (vampire bat) salivary plasminogen activator DSPα1, Alteplase and streptokinase following intravenous bolus injection in a rabbit model of carotid artery thrombosis. Fibrinolysis 1993;7:284–290.
  11. Witt W, Maass B, Baldus B, Hildebrand M, Donner P, Schleuning W-D: Coronary thrombolysis with Desmodus salivary plasminogen activator in dogs. Circulation 1994;90:421–426.
  12. Gulba DC, Praus M, Witt W: DSPA α1-properties of the plasminogen activators of the vampire bat Desmodus rotundus. Fibrinolysis 1995;9:91–96.
  13. Hildebrand M, Bunte T, Bringmann P, Schutt A: Development of an ELISA for the measurement of DSPAα1 (Desmodus rotundus salivary plasminogen activator) in plasma and its application to investigate pharmacokinetics in monkeys. Fibrinolysis 1995;9:107–112.

  

Author Contacts

Wolf-Dieter Schleuning
Paion GmbH, Research Center Berlin, Tegeler Weg 33
D–10589 Berlin (Germany)
Tel. +49 30 34 35 37 12, Fax +49 30 34 35 37 33
E-Mail wd.schleuning@research.paion.de

  

Article Information

Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 0, Number of References : 13

  

Publication Details

Haemostasis (International Journal on Haemostasis and Thrombosis Research)
Official Journal of the ‘Mediterranean League against Thromboembolic Diseases’

Vol. 31, No. 3-6, Year 2001 (Cover Date: May-December 2001 (Released March 2002))

Journal Editor: H.C. Hemker, Maastricht; V.V. Kakkar, London
ISSN: 0301–0147 (print), 1423–0038 (Online)

For additional information: http://www.karger.com/journals/hae


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References

  1. Hawkey C: Plasminogen activator in the saliva of the vampire bat Desmodus rotundus. Nature 1966;211:434–435.

    External Resources

  2. Krätzschmar J, Haendler B, Langer G, Boidol W, Bringmann P, Alagon A, Donner P, Schleuning W-D: The plasminogen activator family from the salivary gland of the vampire bat Desmodus rotundus: Cloning and expression. Gene 1991;105:229–237.
  3. Schleuning W-D, Alagon A, Boidol W, Bringmann P, Petri T, Krätzschmar J, Haendler B, Baldus B, Witt W, Donner P: Plasminogen activators from the saliva of Desmodus rotundus (common vampire bat): Unique fibrin specificity. Ann NY Acad Sci 1992;667:395–403.
  4. Petri T, Langer G, Bringmann P, Cashion L, Shallow S, Schleuning W-D: Production of vampire bat plasminogen activator DSPAα1 in CHO and insect cells. J Biotechnol 1995;39:75–83.

    External Resources

  5. Bringmann P, Gruber D, Liese A, Toschi J, Kraetzschmar J, Schleuning W-D, Donner P: Structural features mediating fibrin selectivity of vampire bat plasminogen activators. J Biol Chem 1995;270:25596–25603.
  6. Renatus M, Stubbs MT, Huber R, Bringmann P, Donner P, Schleuning W-D, Bode W: Catalytic domain structure of vampire bat plasminogen activator: A molecular paradigm for proteolysis without activation cleavage. Biochemistry 1997;36:13483–13493.

    External Resources

  7. Kingston IB, Castro MJ, Anderson S: In vitro stimulation of tissue-type plasminogen activator by Alzheimer amyloid beta-peptide analogues. Nat Med 1995;1:138–142.

    External Resources

  8. Wang YF, Tsirka SE, Strickland S, Stieg PE, Soriano SG, Lipton SA: Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nat Med 1998;4:228–231.
  9. Witt W, Baldus B, Bringmann P, Cashion L, Donner P, Schleuning W-D: Thrombolytic properties of Desmodus rotundus (vampire bat) salivary plasminogen activator in experimental pulmonary embolism in rats. Blood 1992;79:1213–1217.
  10. Muschick P, Zeggert D, Donner P, Witt W: Thrombolytic properties of Desmodus (vampire bat) salivary plasminogen activator DSPα1, Alteplase and streptokinase following intravenous bolus injection in a rabbit model of carotid artery thrombosis. Fibrinolysis 1993;7:284–290.
  11. Witt W, Maass B, Baldus B, Hildebrand M, Donner P, Schleuning W-D: Coronary thrombolysis with Desmodus salivary plasminogen activator in dogs. Circulation 1994;90:421–426.
  12. Gulba DC, Praus M, Witt W: DSPA α1-properties of the plasminogen activators of the vampire bat Desmodus rotundus. Fibrinolysis 1995;9:91–96.
  13. Hildebrand M, Bunte T, Bringmann P, Schutt A: Development of an ELISA for the measurement of DSPAα1 (Desmodus rotundus salivary plasminogen activator) in plasma and its application to investigate pharmacokinetics in monkeys. Fibrinolysis 1995;9:107–112.