Staphylokinase

The staphylokinase gene has been cloned in E. coli, as well as various other recombinant systems. The protein is expressed intracellularly in E. coli at high levels, representing 10-15 per cent of total cellular protein. It can be purified directly from the clarified cellular homogenate by a combination of ion-exchange and hydrophobic interaction chromatography. 

Although staphylokinase shows no significant homology with streptokinase, it induces a thrombolytic effect by a somewhat similar mechanism it also forms a 1 1 stoichiometric complex with plasminogen. The proposed mechanism by which staphylokinase induces plasminogen activation 

CH12 RECOMBINANT BLOOD PRODUCTS AND THERAPEUTIC ENZYMES 

The serum protein a2-antiplasmin can inhibit the activated plasmin-staphylokinase complex. It appears that the a2-antiplasmin can interact with the active plasmin moiety of the complex, resulting in dissociation of staphylokinase and consequent formation of an inactive plasmin-a2-antiplasmin complex. 

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Fibrinolysins are produced by both staphylococci (staphylokinase) and streptococci (streptokinase). These toxins dissolve fibrin clots, formed by the host around wounds and lesions to seal them, by indirect activation of plasminogen, thereby increasing the likelihood of organism spread. Streptokinase m be employed elinieally in conjunction with streptodomase (Chapter 25) in the treatment of thrombosis. 

Staphylokinase (extracted from Staphylococcus aureus and produced in various recombinant systems Various... 

Figure 12.13 Schematic representation of the mechanism by which staphylokinase appears to activate the thrombolytic process via the generation of plasmin. See text for details...

Collen, D. 1998. Staphylokinase a potent, uniquely fibrin-selective thrombolytic agent. Nature Medicine 4(3), 279-284. 

Collen, D. Lijnen, H. (1994). Staphylokinase, a fibrin-specific plasminogen activator with therapeutic potential Blood 84(3), 680-686. 

Collen, D. (1998). Staphylokinase a potent, uniquely fibrin-selective thrombolytic agent. Nature Med. 4(3), 279-284. Collins, R. et al. (1997). Drug therapy—aspirin, heparin and fibrinolytic therapy in suspected acute myocardial infarction. N. Engl. J. Med. 336(12), 847-860. 

Parry, M.A., et ah. The ternary microplasmin-staphylokinase-microplasmin complex is a proteinase-cofactor-substrate complex in action. Nat Struct Biol 1998, 5, 917-923. 

Laroche, Y., et ah, Recombinant staphylokinase variants with reduced antigenicity due to elimination of B-lymphocyte epitopes. Blood 2000, 96, 1425-1432. 

Sakharov, D.V., H.R. Lijnen, D.C. Rijken, Interactions between staphylokinase, plasmin-(ogen), and fibrin. Staphylokinase discriminates between free plasminogen and plasminogen bound to partially degraded fibrin. / Biol Chem 1996, 271, 27912-27918. 

Jespers, L., et ah, Structural and functional basis of plasminogen activation by staphylokinase. Thromb Haemost 1999, 81, 479-485. 

Silence, K., et ah, Structure-function relationships in staphylokinase as revealed by clustered charge to alanine mutagenesis. / Biol Chem 1995, 270, 27192-27198. 

Kim, S.H., et ah, A novel variant of staphylokinase gene from Staphylococcus aureus ATCC 29213. Thromb Res 1997, 87, 387-395. 

Sazonova, I.Y., et al., alpha Domain deletion converts streptokinase into a fibrin-dependent plasminogen activator through mechanisms akin to staphylokinase and tissue plasminogen activator. J Biol Chem 2004, 279, 24994—25001. 

Bedu-Addo, E., Moreadith, R., Advant, S., Preformulation development of recombinant pegylated staphylokinase SY 161 using statistical design, AAPS Pharm., Sci. 4, article 19, 2002, www.aaps.org.. 

PEG MAL-GV-N reverse-phase purification 1414 PEG-staphylokinase, preformulation 1409 Polyethyleneimine 1316... 

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