D2C7-IT is a novel immunotoxin that reacts with wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFRvIII proteins, which has the ability to induce cell death through inhibiting protein synthesis by binding to an elongation factor. Today,
D2C7-IT could be clinically efficacious against brain tumor. Therefore, the study of the structural and functional properties of this drug can be improved the production process.Aim:Hence, the purpose of this study was to determine the structural and functional model of
D2C7-IT immunotoxin as well as the wild-type and mutated form of corresponding receptors in pseudo-physiological conditions.Material and method:In this study, the Protein Atlas database was used to determine the expression of EGFR antigen. The NCBI, Uniprot and RCSB databanks provided the protein sequences and structure of the drug and the antigen. Antigen modeling and fragments assembling of drug were performed by using Modeller software via homology modeling method. ERRAT, Verify 3D and RAMPAGE programs were used for determine the quality of the structure of proteins.
Gromacs program was used to assessment the stability of 3D structure of drug in quasi-physiological condition at 37 ° C. Moreover, the functionality features of the model were performed via its affinity to corresponding antigen and its immunogenicity using HADDOCK and IEDB programs, respectively. The PYMOL software was used to visualize structures and interactionsResult:The expression range of EGFR antigen demonstrated its high expression in a wide range of cancer cells, particularly the liver, skin, stomach, and glioma. In addition, investigation of
D2C7-IT sequencing revealed the presence of monoclonal antibody D2C7-scdsFv and the toxin segment-derived from Pseudomonas exotoxin A. The structural model of EGFR antigen as well as desired quality validation was evaluated. Fragments assembling of drug led to providing several structural models with different quality. Among of them, we have selected the best of them in terms of stability, immunogenicity and optimal performance in real-like condition. In this regard, function verification of the selected model with its negative response to the natural cells antigens was proved.Discussion and conclusion:In conclusion, the results of this study suggested the development of stable structural model of
D2C7-IT immunotoxin drug with potential performance in real-like conditions, which could be an appropriate model for drug optimization and advancement.