Targeted Therapy with a Novel Superantigen-based Fusion Protein Against Interleukin-۱۳ Receptor α۲-overexpressing Tumor Cells: An in-Silico Study
محل انتشار: فصلنامه آسیب شناسی ایران، دوره: 19، شماره: 2
سال انتشار: 1403
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 28
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شناسه ملی سند علمی:
JR_IJP-19-2_007
تاریخ نمایه سازی: 19 اردیبهشت 1403
چکیده مقاله:
Background & Objective: Superantigens are bacterial toxins that induce a massive immune response in the host. Superantigen staphylococcal enterotoxin B (SEB) can form a ternary complex with its receptors, MHC class II (MHCII) and TCR, and can be used in tumor-targeting therapy, particularly when cooperating with a specific vector. In this study, SEB was fused to interleukin-۱۳ (IL۱۳), which forms a complex with IL۱۳ receptor α۲ (IL۱۳Rα۲) overexpressed in glioblastoma multiforme (GBM) cells for therapeutic goals.Methods We designed four fusion proteins based on the arrangement of SEB (N- or C-terminal domain) and provided a flexible inter-domain linker (no or yes), resulting in the formation of SEB-IL۱۳, SEB-L-IL۱۳, IL۱۳-SEB, and IL۱۳-L-SEB, respectively. These fusion proteins were then evaluated for their various physicochemical properties and structural characteristics. Bioinformatics tools were employed to predict, refine, and validate the three-dimensional structure of the fusion proteins. In addition, the fusion proteins were docked with IL۱۳Rα۲, MHCII, and TCR receptors through the HADDOCK ۲.۴ server. The candidate fusion protein was subjected to molecular dynamics simulation.Results: There were differences among the designed fusion proteins. The model with the N-terminal domain of IL۱۳ and containing an inter-domain linker (IL۱۳-L-SEB) was stable and had a long half-life. The docking analysis revealed that the IL۱۳-L-SEB fusion protein had a higher binding affinity to the IL۱۳Rα۲, MHCII, and TCR receptors. Finally, using molecular dynamics simulation through iMODS, acceptable results were obtained for the IL۱۳-L-SEB docked complexes.Conclusion: The results suggest IL۱۳-L-SEB is a promising novel fusion protein for cancer therapeutic application.
کلیدواژه ها:
نویسندگان
Zahra Gholipour
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
Abbas Ali Imani Fooladi
Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
Kazem Parivar
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
Raheleh Halabian
Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
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