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Designing a humanized immunotoxin based on DELTA-stichotoxin-Hmg2a toxin: an in silico study

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Abstract

Breast cancer remains the most frequently diagnosed cancer and the principal cause of mortality by malignancy in women. HER2 positive subtype includes 15–20% of breast cancer cases. This receptor could be an appropriate mark for targeting breast cancer cells. Immunotherapy methods compared to current cancer treatment methods have the lowest side effects. DELTA-stichotoxin-Hmg2a is isolated from the sea anemone and kills cells through pore formation. In the current study, we designed and evaluated an immunotoxin composed of pertuzumab and DELTA-stichotoxin-Hmg2a-derived scFv by bioinformatics tools. The designed immunotoxin was constructed using the amino acid sequences. Then, secondary structure and physico-chemical features were studied, and the tertiary structure of the immunotoxin was built according to the homology modeling methods. The validation and allergenicity of the model were assessed. The immunotoxin and receptor were docked and molecular dynamics simulation indicated the construct stability. The analysis results indicated that the construct is a stable protein that could have a natural-like structure and would not be an allergen, so this immunotoxin could effectively target HER2 receptors. Therefore, our designed immunotoxin could be an appropriate immunotoxin against HER2-positive breast cancer and could be a challenging topic for future in vitro and in vivo studies.

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Funding

This study was financially supported by the Behbahan Faculty of Medical Sciences, Behbahan, Iran (grant number: 400055).

Author information

Author notes

  1. Zeinab Ghesmati and Samira Mokhtari equally contributed to this work and both are first authors.

Authors and Affiliations

  1. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Zeinab Ghesmati

  2. Behbahan Faculty of Medical Sciences, Behbahan, Iran

    Samira Mokhtari, Vahid Zarezade, Zeinab Shajirat & Ahmad Movahedpour

  3. Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Maliheh Parvanak

  4. Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran

    HamidReza Siahkouhi

  5. Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran

    Mortaza Taheri-Anganeh

  6. Infectious and Tropical Diseases Research Center, Research Institute for Health, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

    Khadijeh Ahmadi

  7. Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

    Farzaneh Vahedi

  8. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Navid Nezafat

  9. Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Navid Nezafat

Authors
  1. Zeinab Ghesmati
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  9. Zeinab Shajirat
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  10. Navid Nezafat
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  11. Ahmad Movahedpour
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Contributions

The authors contributed as below:

Writing: Zeinab Ghesmati, Samira Mokhtari, and Maliheh Parvanak; data analysis: Mortaza Taheri-Anganeh, Khadijeh Ahmadi, and Farzaneh Vahedi; critical editing: Vahid Zarezade and Zeinab Shajirat; supervising and conceptualization: Navid Nezafat and Ahmad Movahedpour. All authors reviewed the manuscript.

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Correspondence to Navid Nezafat or Ahmad Movahedpour.

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Ghesmati, Z., Mokhtari, S., Parvanak, M. et al. Designing a humanized immunotoxin based on DELTA-stichotoxin-Hmg2a toxin: an in silico study. J Mol Model 28, 392 (2022). https://doi.org/10.1007/s00894-022-05389-0

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