Design, modeling and simulation of a novel immunotoxin structure affective against gastrointestinal malignancies

Mahsa Saffar kohneh ghouchan,1,* Aliakbar haddad- mashhadrizeh,2 Jamshid mehrzad,3

1. Department of Biology, Islamic Azad University, Khorasan Razavi, Neyshabur, Iran
2. - Cell and molecular biotechnology research group, institute of biotechnology, and Department of Biology, Faculty of Sci
3. - Department of Biology, Islamic Azad University, Khorasan Razavi, Neyshabur, Iran



Gastrointestinal malignancies comprise a remarkable proportion of cancer deaths each year. although many drugs have been developed to overcome this type of malignancies, but they were not really effective so far. therefore, development of new diagnostic and therapeutic procedures are in the center of attention of many research groups. in this regard, developing new immunotoxin drugs aimed specifically at cancer cells is a promising approach


Design, modeling and simulation of new immunotoxin structure affective against these types of malignancies was done by assessing the structural and functional properties of a protein toxin named alphasarcin, as well as analysis of ligands specific to these type of disease antigens


The results of the analysis demonstrated 10 antigens with high expression profile among which gpa33 showed the highest expression and it was specific in colorectal, stomach and pancreatic cancer cells. on the other hand, analyzing protein molecules capable of binding to the selected antigen based on binding affinity, length and post-translational modification parameters led to detection of hsf4 protein molecule and scfva33 monoclonal antibody. assembly of the selected ligand with functional domain of alphasarcin toxin by a flexible linker ggy produced 10 structural model. they were assessed in terms of structural and functional property in pseudo-realistic environment to identify the most stable ones


In general, this study resulted in prediction of a new immunotoxin construct with high structural quality and strong binding affinity to desired antigen in pseudo-realistic environment. studying effectiveness of this construct in experimental and in-vitro tests is the next step ahead of our research group


Malignancy,immunotoxins, antigen, ligand