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Current Topics in Pharmacology   Volumes    Volume 3 
Abstract
Staphylokinase as a new thrombolytic agent
Shigeru Ueshima, Osamu Matsuo
Pages: 77 - 83
Number of pages: 7
Current Topics in Pharmacology
Volume 3 

Copyright © 1997 Research Trends. All rights reserved

ABSTRACT
 
Staphylokinase (SAK) is a profibrinolytic protein, which is produced by Staphylococcus aureus. SAK consists of 136 amino acids with molecular weight of approximately 15,500. Although SAK alone does not have any thrombolytic activity, the complex between SAK and human plasminogen expresses plasminogen activator activity. The conversion of plasminogen to plasmin in complex is required for the expression of plasminogen activator activity. This activity of SAK is inhibited by α2- antiplasmin (α2-AP) immediately. However, in the presence of fibrin, plasmin(ogen) in the complex binds to the fibrin surface via the lysine binding site, and the plasminogen activator activity of SAK is protected against the inhibition by α2-AP. Therefore, SAK revealed fibrin-specific fibrinolytic activity. In animal thrombosis models or clinical studies, SAK showed thrombolytic activity without systemic lytic state. However, antibody-related SAK-neutralizing activity and SAK specific IgG was increased markedly from the second week on and remained elevated for several months. The variant SAKs, whose immunogenicities were impaired by elimination of two of three epitopes, induced fibrin-specific thrombolysis with fewer neutralizing antibody and SAK-specific IgG that wild-type SAK. Thus, SAK is expected as a new thrombolytic agents.
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