Research Themes

• Modification of rattle snake venom derived blood clot dissolver, Alfimeprase, by fusion with C-terminal domain of habu-HR1a and fibrin-targeting peptide
  Grant-in-Aid for Scientific Research (C)
  Teikyo Heisei University
  2011 - 2013
  Alfimeprase(A) can digest fibrin directly, and do not produce any plasmin in different from tPA (Activase). Because A can be rapidly trapped by alpha-2 macroglobulin (alfpha-2M) and inactivated in the blood vein, the clinical effect of A in the phase 2 has not been so good to advance its development. We designed the gene in which the C-terminal side of the A was fused with the C-terminal domain (collagen-binding domain) of the HR1a. Considering targeting to fibrin clots, the C-terminal side of the AH gene was fused with the gene for the human plasminogen-derived kringle domain 1 region, which fusion protein is called AHP. The A, AH and AHP genes were inserted into the pE-SUMO vectors and were expressed in the E.coli BL21(DE3)star. Fusion of the HR1a C-teriminal domain with A did not have any effect in terms of avoiding of inactivation by alpha-2M regardless of the presence or absence of the N-terminal SUMO-peptide.