- Tytuł:
-
Modyfikowane oligodeoksyrybonukleotydy zawierające w wiązaniu internukleotydowym w pozycji mostkowej atom azotu
Modified oligodeoxyribonucleotides containing nitrogen at a bridging position of an internucleotide bond - Autorzy:
- Radzikowska, E.
- Powiązania:
- https://bibliotekanauki.pl/articles/172442.pdf
- Data publikacji:
- 2013
- Wydawca:
- Polskie Towarzystwo Chemiczne
- Tematy:
-
analogi kwasów nukleinowych
modyfikacje wiązania internukleotydowego
oligodeoksyrybonukleozydo-(P3’→N5’)amidofosforany
oligodeoksyrybonukleozydo-(N3’→P5’)amido(tio)fosforany
strategia antysensowa
telomeraza
reakcja Athertona-Todda
nucleic acids analogues internucleotide linkage modifications
oligodeoxyribonucleoside-(P3’→N5’)phosphoramidates
oligodeoxyribonucleoside-
(N3’→P5’)(thio)phosphoramidates antisense strategy
telomerase
Atherton-Todd reaction - Opis:
- Synthetic oligonucleotides (ONs) constitute an important class of compounds which exhibit biological activity. As potential drugs ONs are employed in the antisense strategy [1]. The antisense therapeutic agent acts on the pathogenic mRNA causing inactivation of the target. Ideal antisense agent should be resistant to exo and/or endonucleases, have a suitable pharmacological and pharmacokinetic profile and high affinity for the target. To improve some properties of antisense oligonucleotides plethora of chemical modifications introduced within both sugar unit and internucleotides linkage were investigated. Among numerous ONs modified in internucleotide phosphodiester bond, one of the most interesting are oligonucleotide phosphoramidates (NP-oligos) in which one of the bridging oxygens is replaced by nitrogen atom (at 3’ or 5’ position). Hence, two classes of compounds are formed: oligonucleotide-(N5’→P3’)phosphoramidates and oligonucleotide(N3’→P5’)-phosphoramidates. These compounds, similar to native DNA and RNA, possess an achiral phosphorous atom and all internucleotides bonds are negatively charged. Additionally, NP-oligo shows good resistance to nucleolytic degradation and can bind to the target DNA or RNA with high affinity [12]. In literature several synthetic strategies concerning both (N5’→P3’) and (N3’→P5’) NP-oligos have been described. Some of them allowed to obtain only corresponding dimers. In the light of recent discoveries the most promising candidates for therapeutic and diagnostic applications are oligonucleotide-(N3’→P5’)thiophosphoramidates. Gryaznov et al. have found that such compounds can act as potent and selective telomerase inhibitors [29]. Human telomerase (TA) is a reverse transcriptase ribonucleoprotein that synthesizes de novo d-(TTAGGG)n repeats at chromosomal DNA ends. Whereas activity of this enzyme is observed in ~85% of all human tumors, most of normal somatic cells either lack TA activity or express it only at low levels. For these reasons TA constitute an attractive and nearly universal anticancer target for rational drug development.
- Źródło:
-
Wiadomości Chemiczne; 2013, 67, 11-12; 1003-1025
0043-5104
2300-0295 - Pojawia się w:
- Wiadomości Chemiczne
- Dostawca treści:
- Biblioteka Nauki
Artykuł