Volume 10, Issue 2 (2019)                   JMBS 2019, 10(2): 201-209 | Back to browse issues page

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Sabagh R, Haddad-Mashadrizeh A, Dolatabadi S. Designing and Evaluation of the Structure and Functions of New Immunotoxins for Ovarian Cancer in Quasi-Physiological Conditions. JMBS 2019; 10 (2) :201-209
URL: http://biot.modares.ac.ir/article-22-14617-en.html
1- Biology Department, Science Faculty, Science & Research Branch, Islamic Azad University, Neyshabur, Iran
2- Recombinant Proteins Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran, Institute of Biotechnology, Ferdowsi University of Mashhad, Azadi Square, Mashhad, Iran. Postal Code: 9177948974 , a.haddad@um.ac.ir
3- Microbiology Department, Science Faculty, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran
Abstract:   (7526 Views)
Immunotoxins, as a critical approach for cancer therapy, have ability to induction death in cancerous cells based on specific ligands for targeting cancer-specific antigens and toxin domains in its context. Bearing in mind, discovery the cancer-specific antigens, as well as immunotoxin characterization for modeling based on linkers application, is a critical step for drugs design, which is considered in this study for ovarian cancer based on in-silico biology. The results of this study, led to the detection of 29 antigens with expression capacity on the surface of ovarian cancer cells, with the highest and specific expression associated with MAGE4 and CA125 antigens. Moreover, the 3D structure of MAGE4 was performed, and the pattern of its expression was determined to rely on HLA proteins. On the other hand, among connecting proteins to this antigen TRIM69 selected as the most effective ligand. Subsequently, the assembling between the domain of Corynebacterium diphtheria and this ligand with (GGGGS) 3 linker in 5 positions led to the creation of 50 models, with different quality and structure. However, among these models, S4 drug showed the best structure and function including binding affinity and immunogenicity after simulation in physiological condition. Generally, this result led to present the MAGE4 as a suitable candidate for immunotoxin development for ovarian cancer, as well as an effective immunotoxin which should be considered in an experimental condition.
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Article Type: _ | Subject: Agricultural Biotechnology
Received: 2018/01/23 | Accepted: 2018/04/9 | Published: 2019/06/20

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