Production and functional characteristics of the recombinant targeted toxin based on the HER2-specific non-immunoglobulin scaffold

E. A. Sokolova, A. A. Schulga, O. A. Stremovskiy, I. V. Balalaeva, G. M. Proshkina, S. M. Deyev

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
Pages (from-to)429-434
Number of pages6
JournalBiologicheskie Membrany
Volume33
Issue number6
DOIs
Publication statusPublished - 2016

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Immunotoxins
Ankyrin Repeat
Proteins
Inhibitory Concentration 50
Culture Media
Neoplasms
Research

Keywords

  • HER2 receptor
  • Non-immunoglobulin module darpin
  • Pseudomonas aeruginosa exotoxin A
  • Recombinant targeted toxin
  • Targeted therapy

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Production and functional characteristics of the recombinant targeted toxin based on the HER2-specific non-immunoglobulin scaffold. / Sokolova, E. A.; Schulga, A. A.; Stremovskiy, O. A.; Balalaeva, I. V.; Proshkina, G. M.; Deyev, S. M.

In: Biologicheskie Membrany, Vol. 33, No. 6, 2016, p. 429-434.

Research output: Contribution to journalArticle

Sokolova, E. A. ; Schulga, A. A. ; Stremovskiy, O. A. ; Balalaeva, I. V. ; Proshkina, G. M. ; Deyev, S. M. / Production and functional characteristics of the recombinant targeted toxin based on the HER2-specific non-immunoglobulin scaffold. In: Biologicheskie Membrany. 2016 ; Vol. 33, No. 6. pp. 429-434.
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