[Telomeric oligonucleotide complexes with PGEk protein vector: internalization by target cells and antiproliferative properties].
The recombinant protein PGEk, containing residual of the human epidermal factor (hEGF) bearing DNA binding sequence, retains ability of hEGF to bind with hEGF receptor and to induce cell proliferation was shown. On an example of PGEk complexes with telomeric mimic-oligodeoxyribonucleotide d(TTAGGG)4 and with its thio-analogue we had found such systems can be effectively and selectively internalized by hEGF receptors super expressing cells. The association of this process with a protein/oligonucleotide ratio in complexes was investigated. The intracellular localization of oligonucleotides was explored. We had shown that PGEk not only promotes intensive delivery of oligonucleotides, but also protects them from degradation by nucleases. The oligonucleotides in composition of complexes have considerably more expressed cytotoxic activity in comparison with free oligonucleotides.
Posypanova
G A
GA
Chuvilin
A N
AN
Kireeva
N N
NN
Severin
E S
ES
Pozmogova
G E
GE
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D003603:Cytotoxins / Q000235:genetics / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000235:genetics / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009841:Oligonucleotides / Q000235:genetics / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D016615:Telomere / Q000235:genetics
D003603:Cytotoxins; D004268:DNA-Binding Proteins; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor