Telomeric oligonucleotide complexes with PGEk protein vector: internalization by target cells and antiproliferative properties
Posypanova, G.A.; Chuvilin, A.N.; Kireeva, N.N.; Severin, E.S.; Pozmogova, G.E.
Molekuliarnaia Biologiia 42(2): 286-294
2008
ISSN/ISBN: 0026-8984 PMID: 18610837 Document Number: 617693
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.