Email this article Removal of the translocation domain and the furin cleavage site decreases the relative hepatotoxicity of the targeted antitumor toxins
- Authors: Khodarovich Y.M.1, Konovalova E.V.1, Schulga A.A.1, Deyev S.M.1, Petrov R.V.1
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Affiliations:
- Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
- Issue: Vol 489, No 2 (2019)
- Pages: 209-212
- Section: Biochemistry, biophysics, molecular biology
- URL: https://journals.eco-vector.com/0869-5652/article/view/17949
- DOI: https://doi.org/10.31857/S0869-56524892209-212
- ID: 17949
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Abstract
Targeted toxins are promising anticancer agents that allow selectively destroying cancer cells due to the increased content of onco-specific markers on their surface. The use of such anti-cancer toxins in medicine is mainly hampered by their high non-specific toxicity, in particular, hepatotoxicity. In our work on human cell line, we have shown that the removal of the DARPin-PE40 translocation toxin domain leads to a decrease in hepatoto-xicity. The same effect is also observed when inactivation of the furin cleavage site in the DARPin-PE40 molecule was done. Simultaneous removal of both the translocation domain and the furin cleavage site showed the best results. This toxin modification can be used to create more selective anti-cancer toxins.
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About the authors
Yu. M. Khodarovich
Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
Author for correspondence.
Email: khodarovich@mail.ru
Russian Federation, 16/10, Miklukho-Maklaya Street, Moscow, 117997
E. V. Konovalova
Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
Email: khodarovich@mail.ru
Russian Federation, 16/10, Miklukho-Maklaya Street, Moscow, 117997
A. A. Schulga
Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
Email: khodarovich@mail.ru
Russian Federation, 16/10, Miklukho-Maklaya Street, Moscow, 117997
S. M. Deyev
Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
Email: khodarovich@mail.ru
Russian Federation, 16/10, Miklukho-Maklaya Street, Moscow, 117997
R. V. Petrov
Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
Email: khodarovich@mail.ru
Academician of the Russian Academy of Sciences
Russian Federation, 16/10, Miklukho-Maklaya Street, Moscow, 117997References
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