article information

International Journal of Cancer Management: Vol.7, issue 3; e80546
published online: September 30, 2014
article type: Research Article
received: April 22, 2014
accepted: June 25, 2014

In Silico Design and Analysis of TGFαL3-SEB Fusion Protein as “a New Antitumor Agent” Candidate by Ligand-Targeted Superantigens Technique

authors:

avatar Abbas Ali Imani-Fooladi 1 , avatar Forough Yousefi 2 , avatar Seyed Fazloallah Mousavi 2 , avatar Jafar Amani 1 , *

Applied Microbiology Research center, Baqiyatallah University of Medical Sciences, Tehran, Iran
Dept. of Bacteriology, Pasteur Institute of Iran, Tehran, Iran

how to cite: Imani-Fooladi A A, Yousefi F, Mousavi S F, Amani J . In Silico Design and Analysis of TGFαL3-SEB Fusion Protein as “a New Antitumor Agent” Candidate by Ligand-Targeted Superantigens Technique. Int J Cancer Manag. 2014;7(3):e80546. 

Abstract

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

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