Abstract
Designing of new high-affinity protein compounds that can selectively destroy human cancer cells is a priority research area in biomedicine. In this work we report on the production procedure and describe functional characteristics of genetically encoded targeted toxin DARPin-PE40 for selective destruction of HER2-positive human cancer cells. HER2-specific non-immunoglobulin scaffold protein with ankyrin repeat was used as a targeting moiety. As a cytotoxic module, we used a fragment of the Pseudomonas exotoxin A. Using cytoplasmic expression in a bacterial system, we produced a monomelic protein with the yield of 180 mg per 1 L of culture medium. It was shown that targeted recombinant toxin possesses a considerable cytotoxic activity in vitro against HER2-positive cells (IC50 2 pM).
Original language | English |
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Pages (from-to) | 429-434 |
Number of pages | 6 |
Journal | Biologicheskie Membrany |
Volume | 33 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2016 |
Keywords
- HER2 receptor
- Non-immunoglobulin module darpin
- Pseudomonas aeruginosa exotoxin A
- Recombinant targeted toxin
- Targeted therapy
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology