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Wyświetlanie 1-2 z 2
Tytuł:
Antisense hairpin loop oligonucleotides as inhibitors of expression of multidrug resistance-associated protein 1: Their stability in fetal calf serum and human plasma.
Autorzy:
Rębowski, Grzegorz
Wójcik, Marzena
Boczkowska, Małgorzata
Gendaszewska, Edyta
Soszyński, Mirosław
Bartosz, Grzegorz
Niewiarowski, Wojciech
Powiązania:
https://bibliotekanauki.pl/articles/1044049.pdf
Data publikacji:
2001
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
human plasma
3' -exonuclease activity
multidrug resistance-associated protein
fetal calf serum
antisense hairpin loop oligonucleotides
Opis:
Multidrug resistance-associated protein (MRP1) is a transmembrane pump protein responsible for the efflux of chemotherapeutic drugs, an important cause of anticancer treatment failure. Trying to circumvent MRP-mediated resistance we designed and synthesized hairpin loops forming antisense oligodeoxyribonucleotides (ODNs), both phosphodiesters (PO-ODNs) and their phosphorothioate analogues (PS-ODNs), to reduce the protein expression by targeting its mRNA in a sequence specific manner. Melting temperature measurements as well as polyacrylamide gel electrophoresis supported the preferential formation of a secondary structure, which was expected to protect ODNs against 3'-exonuclease degradation. ODNs and PS-ODNs designed in this work were successfully tested as antisense inhibitors of the expression of MRP1 in the leukaemia HL60/ADR cell line. Foreseeing the necessity to perform clinical studies with such ODNs we investigated their stability against the 3'-exonuclease activity of fetal calf serum and human plasma. Under the conditions, corresponding to physiological ones, we observed high stability of hairpin loop forming ODNs, especially those containing longer (e.g. 7 base pair) stems. Comparative studies on the stability of chemically unmodified hairpin loop forming ODNs and their PS-counterparts indicated that endonuclease activity did not play any important role in the process of their nucleolytic degradation. Our studies provide strong evidence for high stability of chemically unmodified hairpin loop ODNs, making them an attractive alternative to phosphorothioate analogues commonly used in antisense strategy.
Źródło:
Acta Biochimica Polonica; 2001, 48, 4; 1061-1076
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Multidrug resistance-associated protein - reduction of expression in human leukaemia cells by antisense phosphorothioate olignucleotides.
Autorzy:
Niewiarowski, Wojciech
Gendaszewska, Edyta
Rębowski, Grzegorz
Wójcik, Marzena
>Mikołajczyk, Barbara
Soszyński, Mirosław
Bartosz, Grzegorz
Powiązania:
https://bibliotekanauki.pl/articles/1044273.pdf
Data publikacji:
2000
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
antisense oligonucleotides
MRP
multidrug resistance
Opis:
Multidrug resistance-associated protein (MRP1) causes cellular drug resistance in several cancer cell lines. In this paper we show that antisense oligonucleotides decrease MRP1 expression in human leukaemia cells. We investigated biological activity of a series of 12 linear phosphorothioate oligonucleotides, complementary to several regions of MRP1 mRNA. The oligonucleotides were administered to leukaemia HL60/ADR cells overexpressing MRP1 protein. Then, the level of MRP1 mRNA was determined by means of semiquantitative RT-PCR and the protein level by reaction with specific monoclonal antibodies. Some of the investigated antisense oligonucleotides decrease the expression level of the MRP1 protein by 46% and its mRNA level by 76%.
Źródło:
Acta Biochimica Polonica; 2000, 47, 4; 1183-1188
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
    Wyświetlanie 1-2 z 2

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