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Removal of the Translocation Domain and the Furin Cleavage Site Decreases the Relative Hepatotoxicity of the Targeted Antitumor Toxins

  • BIOCHEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
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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 hepatotoxicity. 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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Funding

The study was supported by the Russian Foundation for Basic Research (project no. 18-04-00212 A). Work on the isolation and purification of targeted toxins was supported by the Russian Science Foundation (project no. 19-14-00112). Work of E.V. Konovalova was supported by the Russian Foundation for Basic Research (project no. 183400899 mol-a).

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Authors and Affiliations

  1. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia

    Yu. M. Khodarovich, E. V. Konovalova, A. A. Schulga, S. M. Deyev &  R. V. Petrov

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  1. Yu. M. Khodarovich
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  2. E. V. Konovalova
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  3. A. A. Schulga
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  4. S. M. Deyev
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  5. R. V. Petrov
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Corresponding author

Correspondence to Yu. M. Khodarovich.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Translated by M. Batrukova

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Khodarovich, Y.M., Konovalova, E.V., Schulga, A.A. et al. Removal of the Translocation Domain and the Furin Cleavage Site Decreases the Relative Hepatotoxicity of the Targeted Antitumor Toxins. Dokl Biochem Biophys 489, 370–372 (2019). https://doi.org/10.1134/S1607672919060048

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  • DOI: https://doi.org/10.1134/S1607672919060048

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