Staphylokinase-annexin XI chimera exhibited efficient in vitro thrombolytic activities

Jeng Fong Chiou, Ming Dar Woon, Shin Nan Cheng, Chih Hsueng Hsu, Shiou Chi Cherng, Feng Ken Hsieh, Shou Ming Lin, Chia Yang Shiau

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Abstract

Annexins (ANXs) are a family of calcium dependent phospholipid binding proteins. Phospholipids such as phosphatidylserine are rapidly exposed on the surfaces of injured endothelial cells, activated platelets, and apoptotic cells in a large number of disorders. In this study, annexin V and XI (ANXV and ANXXI) were individually fused to the C-terminal of staphylokinase (SAK), a fibrin-selective thrombolytic protein, to form chimeras for evaluation of their in-vitro thrombolytic activities. The two chimeras were found to have plasminogen activation activity of comparable efficiency. When the chimeras were challenged under higher concentrations of plasmin for 1 h, hydrolysis of them into moieties was not seen on SDS-PAGE. In two thrombolytic assays, SAK-ANXXI was found to resolve both platelet rich plasma (PRP) clots and platelet poor plasma (PPP) clots with an efficiency similar to that of SAK. However, SAK-ANXV showed significantly reduced efficiency. With regard to anticoagulation ability, SAK-ANXXI was also found to have a stronger effect on dose-dependent extension of clotting time among the four tested proteins. The unique long N-terminal tail of ANXXI, composed of 202 residues, in contrast to the 16 residues of ANXV, probably served successfully to dispatch two moieties to function properly in a complicated microenvironment. Hence, a new option other than the most committed ANXV for the ANX based chimera without elaboration of linker construction is presented.

Original languageEnglish
Pages (from-to)1122-1129
Number of pages8
JournalBioscience, Biotechnology and Biochemistry
Volume71
Issue number5
DOIs
Publication statusPublished - 2007

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Keywords

  • Annexin
  • Chimera
  • Staphylokinase
  • Thrombolytic

ASJC Scopus subject areas

  • Bioengineering
  • Biotechnology
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry (miscellaneous)
  • Applied Microbiology and Biotechnology
  • Food Science

Cite this

Chiou, J. F., Woon, M. D., Cheng, S. N., Hsu, C. H., Cherng, S. C., Hsieh, F. K., Lin, S. M., & Shiau, C. Y. (2007). Staphylokinase-annexin XI chimera exhibited efficient in vitro thrombolytic activities. Bioscience, Biotechnology and Biochemistry, 71(5), 1122-1129. https://doi.org/10.1271/bbb.60279