Synthesis and properties of 2'-deoxy-2',4'-difluoroarabinose-modified nucleic acids.
Synthesis and properties of 2'-deoxy-2',4'-difluoroarabinose-modified nucleic acids.
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DOI：
10.1021/jo502948t
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发表时间：
2015-03-20
期刊：
影响因子：
--
通讯作者：
Damha MJ
中科院分区：
文献类型：
--
作者：
Martínez-Montero S;Deleavey GF;Dierker-Viik A;Lindovska P;Ilina T;Portella G;Orozco M;Parniak MA;González C;Damha MJ
我们报道了2′-脱氧-2 ′，4 ′-二氟阿拉伯糖修饰的核酸的合成、热稳定性和RNase H底物活性。以2 ′-脱氧-2 ′，4 ′-二氟阿拉伯尿苷（2，′4′-diF-araU）为原料，经6步反应合成了2 ′-脱氧-2 ′，4 ′-二氟阿拉伯尿苷（2，′ 4 ′-diF-araU）。在核苷水平上的NMR分析和量子力学计算表明，尽管2′-βF的存在通常会使糖褶皱转向南/东构象，但4′-氟的引入会导致向北构象的强烈偏向。将新单体掺入DNA导致对DNA-RNA杂交体的中性至轻微稳定的热效应。与全DNA链或含有相应2′-F-araU核苷酸单元的DNA链相比，在DNA-RNA杂合体的DNA链中插入2′，4 ′-diF-araU核苷酸降低了人和HIV逆转录酶相关的RNA酶H介导的补体RNA链的切割速率，这与2′-F-araU中的4′-氟将优选的糖构象从DNA样（南/东）转换为RNA样（北）的概念一致。
We report the synthesis, thermal stability, and RNase H substrate activity of 2′-deoxy-2′,4′-difluoroarabino-modified nucleic acids. 2′-Deoxy-2′,4′-difluoroarabinouridine (2,′4′-diF-araU) was prepared in a stereoselective way in six steps from 2′-deoxy-2′-fluoroarabinouridine (2′-F-araU). NMR analysis and quantum mechanical calculations at the nucleoside level reveal that introduction of 4′-fluorine introduces a strong bias toward the North conformation, despite the presence of the 2′-βF, which generally steers the sugar pucker toward the South/East conformation. Incorporation of the novel monomer into DNA results on a neutral to slightly stabilizing thermal effect on DNA–RNA hybrids. Insertion of 2′,4′-diF-araU nucleotides in the DNA strand of a DNA–RNA hybrid decreases the rate of both human and HIV reverse transcriptase-associated RNase H-mediated cleavage of the complement RNA strand compared to that for an all-DNA strand or a DNA strand containing the corresponding 2′-F-araU nucleotide units, consistent with the notion that a 4′-fluorine in 2′-F-araU switches the preferred sugar conformation from DNA-like (South/East) to RNA-like (North).
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影响因子：
15
作者：
Anzahaee, Maryam Yahyaee;Watts, Jonathan K.;Damha, Masad J.
通讯作者：
Damha, Masad J.
影响因子：
2.1
作者：
HAASNOOT, CAG;DELEEUW, FAAM;ALTONA, C
通讯作者：
ALTONA, C
影响因子：
3
作者：
Gong, Qingguo;Menon, Lakshmi;Ishima, Rieko
通讯作者：
Ishima, Rieko
影响因子：
15
作者：
ALTONA, C;SUNDARALINGAM, M
通讯作者：
SUNDARALINGAM, M
影响因子：
15
作者：
Noy, A;Pérez, A;Orozco, M
通讯作者：
Orozco, M