Evaluation of In vivo Bioactivity of a Mutated Streptokinase

• Main Authors: Marzieh Sameni, Mazaher Gholipourmalekabadi, Mojgan Bandehpour, Mehrdad Hashemi, Farzin Sahebjam, V Tohidi, Bahram Kazemi
• Format: Article
• Language: English
• Published: Shahid Beheshti University of Medical Sciences 2017-04-01
• Series: Novelty in Biomedicine
• Subjects: Thrombolysis; Recombinant streptokinase; Thrombolytic agent; Fibrinolytic activity; Jugular vein; Clot formation
• Online Access: http://journals.sbmu.ac.ir/nbm/article/view/13694

<br /><p> </p><h2>Background: Immunogenicity of Streptokinase, as a thrombolytic drug, has limited its clinical use. Elimination of the amino acid residues that are responsible for immunogenicity while don’t affect the bioactivity of streptokinase is worthy. Recently, we modified the streptokinase through the elimination of 42 amino acids from its’ C-terminal and assessed its bioactivity in vitro. In this study, bioactivity of the mutated-streptokinase determined and compared with those of commercially available streptokinase (Heberkinase) in rabbits with induced blood clot.</h2><p><strong>M</strong><strong>aterials and Methods:</strong> . Recombinant mutated streptokinase was purified and its lipopolysaccharide  contained  remove and evaluated by LAL test. Thrombolytic activity of drug was evaluated by rabbit jugular vein as in vivo thrombosis model<em>. </em>The thrombolytic property of the drug was evaluated with determining of D-dimer in plasma.</p><p><strong>R</strong><strong>es</strong><strong>ults:</strong>. The results showed in vivo bioactivity of both truncated and commercial streptokinase (p&lt;0.05). This study showed an important influence of the 42 amino acids of C-terminal in bioactivity of the streptokinase.</p><p><strong>Conclusion: </strong>Clinical use of the r-streptokinase requires more modification to restore its’ activity in vivo. This product may be a promising choice for clinical use after confirmation of its stability and non-immunogenicity.</p>