Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 
  • Users Online: 355
  • Home
  • Print this page
  • Email this page
ORIGINAL ARTICLE
Year : 2023  |  Volume : 18  |  Issue : 2  |  Page : 159-176

A comparative study of the arazyme-based fusion proteins with various ligands for more effective targeting cancer therapy: an in-silico analysis


1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, I.R. Iran
2 Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, I.R. Iran

Correspondence Address:
Abbas Ali Imani Fooladi
Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Tel & Fax: +98-2188068924
I.R. Iran
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1735-5362.367795

Rights and Permissions

Background and purpose: Recently, the use of immunotoxins for targeted cancer therapy has been proposed, to find new anticancer drugs with high efficacy on tumor cells with minimal side effects on normal cells. we designed and compared several arazyme (AraA)-based fusion proteins with different ligands to choose the best-targeted therapy for interleukin 13 receptor alpha 2 (IL13Rα2)-overexpressed cancer cells. For this purpose, IL13Rα2 was selected as a receptor and IL13 and IL13.E13K were evaluated as native and mutant ligands, respectively. In addition, Pep-1 and A2b11 were chosen as the peptide ligands for targeted cancer therapy. Experimental approach: Several bioinformatics servers were used for designing constructs and optimization. The structures of the chimeric proteins were predicted and verified by I-TASSER, Q-Mean, ProSA, Ramachandran plot, and Verify3D program. Physicochemical properties, toxicity, and antigenicity were predicted by ProtParam, ToxinPred, and VaxiJen. HawkDock, LigPlot+, and GROMACS software were used for docking and molecular dynamics simulation of the ligand-receptor interaction. Findings/Results: The in silico results showed AraA-A2b11 has higher values of confidence score and Q-mean score was obtained for high-resolution crystal structures. All chimeric proteins were stable, non-toxic, and non-antigenic. AraA-(A(EAAAK)4ALEA(EAAAK)4A)2-IL13 retained its natural structure and based on ligand-receptor docking and molecular dynamic analysis, the binding ability of AraA-(A(EAAAK)4ALEA(EAAAK)4A)2-IL13 to IL13Rα2 was sufficiently strong. Conclusion and implications: Based on the bioinformatics result AraA-(A(EAAAK)4ALEA(EAAAK)4A)2-IL13 was a stable fusion protein with two separate domains and high affinity with the IL13Rα2 receptor. Therefore, AraA-(A(EAAAK)4ALEA(EAAAK)4A)2-IL13 fusion protein could be a new potent candidate for target cancer therapy.


[FULL TEXT] [PDF]*
Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed206    
    Printed0    
    Emailed0    
    PDF Downloaded29    
    Comments [Add]    

Recommend this journal