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.

中文翻译：

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去除易位域和弗林蛋白酶切割位点降低了靶向抗肿瘤毒素的相对肝毒性。

摘要

靶向毒素是有前途的抗癌剂，由于其表面上癌特异性标记物含量的增加，可以选择性破坏癌细胞。这种抗癌毒素在医学中的使用主要受到其高的非特异性毒性，特别是肝毒性的阻碍。在我们对人类细胞系的研究中，我们发现DARPin-PE40易位毒素域的去除导致肝毒性的降低。当完成DARPin-PE40分子中弗林蛋白酶切割位点的灭活时，也观察到相同的效果。同时去除易位域和弗林蛋白酶切割位点显示了最好的结果。这种毒素修饰可用于产生更具选择性的抗癌毒素。