Evaluation of In vivo Bioactivity of a Mutated Streptokinase

Novelty in Biomedicine

Bahram Kazemi¹  Mojgan Bandehpour¹  Mazaher Gholipourmalekabadi¹  Marzieh Sameni²  Farzin Sahebjam³  V Tohidi³  Mehrdad Hashemi⁴ 

[1] Cellular and Molecular Biology Research Center andBiotechnology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;Department of Biology, Faculty of Basic Sciences, Science and Research Branche, Islamic Azad University, Tehran, Iran;Department of Clinical Science, Faculty of Veterinary Medicine, Karaj Branch, Islamic Azad University, Karaj, Iran;Department of Genetics, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran;

关键词: Thrombolysis;    Recombinant streptokinase;    Thrombolytic agent;    Fibrinolytic activity;    Jugular vein;    Clot formation;   

DOI  :  

来源: DOAJ

【 摘 要 】

 

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.

Materials and Methods: . 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. The thrombolytic property of the drug was evaluated with determining of D-dimer in plasma.

Results:. The results showed in vivo bioactivity of both truncated and commercial streptokinase (p<0.05). This study showed an important influence of the 42 amino acids of C-terminal in bioactivity of the streptokinase.

Conclusion: 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.

【 授权许可】

Unknown