Staphylokinase: Biochemistry And Pharmacodynamics

  • Steven Vanderschueren
  • Désiré Collen
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 193)


Although the existence of staphylokinase (Sak) has been known since at least 1908 [1], detailed biochemical evaluation and clinical testing of Sak have only recently been initiated. Staphylokinase is a 136 amino acid protein, made of a single polypeptide chain without disulfide bridges (Figure 18-1), secreted by Staphylococcus aureus strains after transformation with bacteriophages or after lysogenic conversion. The production of Sak by S. aureus is believed to play a role in tissue penetration and in invasion by the bacteria [2]. The structure of Sak shows no homology with that of other plasminogen activators. Three natural variants that have been characterized (SakSTAR, Sak42D, and SakφC) [3, 4, 5] differ at amino acid positions 34, 36, and 43 (Table 18-1), and have a similar plasminogen-activating potential but different thermostability [6].


Clot Lysis Coronary Thrombolysis Peripheral Arterial Occlusion Fibrin Specificity Fibrin Surface 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Much H. Über eine Vorstufe des Fibrinfermentes in Kulturen von Staphylokokkus aureus. Biochemische Zeitschrift 14:143, 1908.Google Scholar
  2. 2.
    Mölkänen T, Kuikka T, Kuusela P. Production of staphylokinase by staphylococcus strains isolated from bacteremic patients (abstr). Fibrinolysis 10(Suppl. 3):138, 1996.Google Scholar
  3. 3.
    Sako T, Tsuchida N. Nucleotide sequence of the staphylokinase gene from Staphylococcus aureus. Nucleic Acids Res 11:7679, 1983.PubMedCrossRefGoogle Scholar
  4. 4.
    Behnke D, Gerlach D. Cloning and expression in Escherichia coli, Bacillus subtilis and Streptococcus sanguis of a gene for staphylokinase: A bacterial plasminogen activator. Mol Gen Genet 210:528, 1987.PubMedCrossRefGoogle Scholar
  5. 5.
    Collen D, Zhao ZA, Holvoet P, Marynen P. Primary structure and gene structure of staphylokinase. Fibrinolysis 6:226, 1992.CrossRefGoogle Scholar
  6. 6.
    Gase A, Birch-Hirschfeld E, Gührs KH, Hartmann M, Vetterman S, Damaschun G, Damaschun H, Gast K, Misselwitz R, Zirwer D, Collen D, Schlott B. The thermostability of natural variants of bacterial plasminogen-activator staphylokinase. Eur J Biochem 223:303, 1994.PubMedCrossRefGoogle Scholar
  7. 7.
    Schlott B, Hartmann M, Gührs KH, Birsch-Hirschfeld E, Pohl D, Vanderschueren S, Van de Werf F, Michoel A, Collen D, Behnke D. High yield production and purification of recombinant staphylokinase for thrombolytic therapy. Biotechnology 12:185, 1994.PubMedCrossRefGoogle Scholar
  8. 8.
    Collen D, Lijnen HR. Staphylokinase, a fibrin-specific plasminogen activator with therapeutic potential? Blood 84:680, 1994.PubMedGoogle Scholar
  9. 9.
    Lijnen HR. Staphylokinase. In Handbook of Experimental Pharmacology. Fibrinolytics and Antifibrinolytics. Heidelberg: Springer Verlag, in press.Google Scholar
  10. 10.
    Vanderschueren SMF, Lijnen HR, Collen D. Properties of staphylokinase and its potential as a thrombolytic agent. Fibrinolysis (Suppl. 1):87, 1995.Google Scholar
  11. 11.
    Lijnen HR, Van Hoef B, Vandenbossche L, Collen D. Biochemical properties of natural and recombinant staphylokinase. Fibrinolysis 6:214, 1992.CrossRefGoogle Scholar
  12. 12.
    Lijnen HR, Van Hoef B, Collen D. Interactions of staphylokinase with human platelets. Thromb Haemost 73:472, 1995.PubMedGoogle Scholar
  13. 13.
    Vanderschueren S, Collen D. Comparative effects ot staphylokinase and alteplase in rabbit bleeding rime models. Thromb Haemost 75:816, 1996.PubMedGoogle Scholar
  14. 14.
    Lijnen HR, Stassen JM, Collen D. Differential inhibition with antifibrinolytic agents of staphylokinase and streptokinase induced clot lysist. Thromb Haemosr 73:845, 1995.Google Scholar
  15. 15.
    Collen D, De Cock F, Van Linthout J, Declerck PJ, Lijnen HR, Stassen JM. Comparative thrombolytic and immunogenic properties of staphylokinase and streptokinase. Fibrinolysis 6:232, 1992.CrossRefGoogle Scholar
  16. 16.
    Collen D, De Cock F, Stassen JM. Comparative immunogenicity and thrombolytic properties toward arterial and venous thrombi of streptokinase and recombinant staphylokinase in baboons. Circulation 87:996, 1993.PubMedGoogle Scholar
  17. 17.
    Collen D, Van de Werf F. Coronary thrombolysis with recombinant staphylokinase in patients with evolving myocardial infarction. Circulation 87:1850, 1993.PubMedGoogle Scholar
  18. 18.
    Collen DC, Gold HK. New developments in thrombolyttc therapy. Adv Exp Med Biol. 281:333, 1990.PubMedGoogle Scholar
  19. 19.
    Vanderschueren S, Barrios L, Kerdsinchai P, Van den Heuvel P, Hermans L, Vrolix M, De Man F, Benit E, Muyldermans L, Collen D, Van de Werf F. A randomized trial of recombinant staphylokinase versus alteplase for coronary artery patency in acute myocardial infarction. Circulation 92:2044, 1995.PubMedGoogle Scholar
  20. 20.
    Vanderschueren S, Collen D, Van de Werf F. A pilot study on bolus administration of recombinant staphylokinase for coronary artery thrombolysis. Thromb Haemost 76:541, 1996.PubMedGoogle Scholar
  21. 21.
    Vanderschueren S, Dens J, Kerdsinchai P, Desmet W, Vrolix M, De Man F, Van den Heuvel P, Hermans L, Collen D, Van de Werf F. A pilot randomized coronary patency trial of double-bolus recombinant staphylokinase versus front-loaded alteplase in acute myocardial infarction. Am Heart, in press.Google Scholar
  22. 22.
    Vanderschueren S, Stockx L, Wilms G, Verhaeghe R, Lacroix H, Vermylen J, Collen D. Thrombolytic therapy of peripheral arterial occlusion with recombinant staphylokinase. Circulation 92:2050, 1995.PubMedGoogle Scholar
  23. 23.
    Vanderschueren SMF, Stassen JM, Collen D. On the immunogenicity of recombinant staphylokinase in patients and in animal models. Thromb Haemost 72:297, 1994.PubMedGoogle Scholar
  24. 24.
    Declerck PJ, Vanderschueren S, Billiet J, Moreau H, Collen D. Prevalence and induction of circulating antibodies against recombinant staphylokinase. Thromb Haemost 71:129, 1994.PubMedGoogle Scholar
  25. 25.
    Collen D, Bernaerts R, Declerck P, De Cock F, Demarsin E, Jenné S, Laroche Y, Lijnen HR, Silence K, Verstreken M. Recombinant staphylokinase variants with altered immunoreactivity. I. Construction and characterization. Circulation 94:197, 1996.PubMedGoogle Scholar
  26. 26.
    Collen D, Moreau H, Stockx L, Vanderschueren S. Recombinant staphylokinase variants with altered immunoreactivity. II. Thrombolytic properties and antibody induction. Circulation 94:207, 1996.PubMedGoogle Scholar
  27. 27.
    Vanderschueren S, Stassen JM, Collen D. Comparative antigenicity of wild-type staphylokinase (SakSTAR) and a selected mutant (SakSTAR.M38) in a baboon thrombolysis model. J Cardiovasc Pharmacol 27:809, 1996.PubMedCrossRefGoogle Scholar
  28. 28.
    Collen D, De Cock F, Demarsin E, Jenné S, Lasters I, Laroche Y, Warmerdam P, Jespers L. Recombinant staphylokinase variants with altered immunoreactivity. III. Species variability of antibody binding patterns. Circulation 95:455, 1997.PubMedGoogle Scholar
  29. 29.
    Collen D, Stockx L, Lacroix H, Suy R, Vanderschueren S. Recombinant staphylokinase variants with altered immunoreactivity. IV. Identification of variants with reduced antibody induction but intact potency. Circulation 95:463, 1997.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Steven Vanderschueren
  • Désiré Collen

There are no affiliations available

Personalised recommendations