19 F NMR Spectroscopic Analysis of the Binding Modes in Triple-Helical Peptide Nucleic Acid (PNA)/MicroRNA Complexes.

19 F NMR Spectroscopic Analysis of the Binding Modes in Triple-Helical Peptide Nucleic Acid (PNA)/MicroRNA Complexes.
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三螺旋肽核酸 (PNA)/MicroRNA 复合物中结合模式的 19 F NMR 光谱分析。

DOI:
10.1002/chem.201700601
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发表时间:
2017
期刊:
影响因子:
--
通讯作者:
P. Virta
P. Virta
中科院分区:
--
文献类型:
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作者:
Ville Tähtinen;Lotta Granqvist;M. Murtola;R. Strömberg;P. Virta

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三链体形成肽核酸 (TFPNA) 靶向 19 F 标记的 RNA 发夹模型(具有六乙二醇 (heg) 环的富含 UA 的双链体和 microRNA 模型 miR-215)的双螺旋区域。除了传统的基于紫外和圆二色性 (CD) 的检测之外,还通过 19 F NMR 光谱监测结合。可以获得有关三螺旋肽核酸 (PNA)/RNA 和 (PNA)2/RNA 结合模式之间的化学计量和转变的详细信息。另外合成了TFPNA的γ-(R)-羟甲基修饰的胸腺嘧啶-1-基-和2-氨基吡啶-3-基-乙酰基衍生物,其靶向相同的RNA模型,并研究了γ-(R)-羟甲基基团对结合的影响。 γ-(R)-羟甲基修饰的适当模式降低了三元复合物的稳定性以及与 miR-215 模型的优选化学计量结合。
Triplex-forming peptide nucleic acids (TFPNAs) were targeted to double-helical regions of 19 F-labeled RNA hairpin models (a UA-rich duplex with a hexaethylene glycol (heg) loop and a microRNA model, miR-215). In addition to conventional UV- and circular dichroism (CD)-based detection, binding was monitored by 19 F NMR spectroscopy. Detailed information on the stoichiometry and transition between the triple-helical peptide nucleic acid (PNA)/RNA and (PNA)2 /RNA binding modes could be obtained. γ-(R)-Hydroxymethyl-modified thymine-1-yl- and 2-aminopyridin-3-yl-acetyl derivatives of TFPNAs were additionally synthesized, which were targeted to the same RNA models, and the effect of the γ-(R)-hydroxymethyl group on binding was studied. An appropriate pattern of γ-(R)-hydroxymethyl modifications reduced the stability of the ternary complex and preferred stoichiometric binding to the miR-215 model.
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