in silico design and analysis of tgfαl3-seb fusion protein as “a new antitumor agent” candidate by ligand-targeted superantigens technique

background: bacterial superantigen staphylococcal enterotoxins (ses), has stimulated polyclonal t cells irrespective of their antigen specificity, resulted a massive release of cytokines, and suggested that they could be assigned as a candidate of new antitumor agents. recent attempts have done to specifically target superantigens towards tumors, subsequently monoclonal antibodies and tumor-related ligands have employed as targeting molecules of superantigen for the preclinical treatment of different tumors. here, we have evaluated tgfαl3-seb fusion protein as a new antitumor candidate by genetically fusing the third loop of transforming growth factor alpha (tgfαl3) to staphylococcal enterotoxin type b. methods: an in silico techniques have launched to characterize the properties and structure of the protein, before initiating the experimental study, we have predicted physicochemical properties, structures, stability, mhc binding properties and ligand-receptor interaction of this chimeric protein by means of computational bioinformatics tools and servers. results: our results have indicated codon adaptation index of tgfαl3-seb fusion gene has increased from 0.5 in the wild type sequences to 0.85 in the chimeric optimized gene. the mfold data has shown the tgfαl3-seb mrna was stable enough for efficient translation in the new host. based on ramachandran plot tgfαl3-seb   has classified as a stable fusion protein. our result has shown fusing of tgfal3 in n-terminal of the tgfαl3-seb construct, had no effects on mhc binding and subsequently superantigenic activity of seb. finally based on ligand-receptor docking the binding ability of tgfal3 was strong enough to its receptor, so tgfαl3-seb could be assigned as a new antitumor candidate in cancer immunotherapy. conclusion: our results have proposed that tgfαl3-seb was a stable fusion protein with proper affinity to its receptor that overexpressed in various human carcinomas, so it could generate potent immune response towards tumors.   please cite this article as: imani fooladi aa, yousefi f, mousavi sf, amani j. in silico design and analysis of tgfαl3-seb fusion protein as “a new antitumor agent” candidate by ligand-targeted superantigens technique. iran j cancer prev. 2014; 7(3):152-64.