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 |
|---|---|
| Pages (from-to) | 429-434 |
| Number of pages | 6 |
| Journal | Biologicheskie Membrany |
| Volume | 33 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2016 |
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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 journal › Article
}
TY - JOUR
T1 - Production and functional characteristics of the recombinant targeted toxin based on the HER2-specific non-immunoglobulin scaffold
AU - Sokolova, E. A.
AU - Schulga, A. A.
AU - Stremovskiy, O. A.
AU - Balalaeva, I. V.
AU - Proshkina, G. M.
AU - Deyev, S. M.
PY - 2016
Y1 - 2016
N2 - 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).
AB - 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).
KW - HER2 receptor
KW - Non-immunoglobulin module darpin
KW - Pseudomonas aeruginosa exotoxin A
KW - Recombinant targeted toxin
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85016049504&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85016049504&partnerID=8YFLogxK
U2 - 10.7868/S0233475516060116
DO - 10.7868/S0233475516060116
M3 - Article
VL - 33
SP - 429
EP - 434
JO - Biologicheskie Membrany
JF - Biologicheskie Membrany
SN - 0233-4755
IS - 6
ER -