Recent findings in cell biology have rekindled interest in Z-DNA, the left-handed helical form of DNA. We report here that two minimally modified nucleosides, 2′F-araC and 2′F-riboG, induce the formation of the Z-form under low ionic strength. We show that oligomers entirely made of these two nucleosides exclusively produce left-handed duplexes that bind to the Zα domain of ADAR1. The effect of the two nucleotides is so dramatic that Z-form duplexes are the only species observed in 10 mM sodium phosphate buffer and neutral pH, and no B-form is observed at any temperature. Hence, in contrast to other studies reporting formation of Z/B-form equilibria by a preference for purine glycosidic angles in syn, our NMR and computational work revealed that sequential 2′F…H2N and intramolecular 3′H…N3′ interactions stabilize the left-handed helix. The equilibrium between B- and Z- forms is slow in the 19F NMR time scale (≥ms), and each conformation exhibited unprecedented chemical shift differences in the 19F signals. This observation led to a reliable estimation of the relative population of B and Z species and enabled us to monitor B–Z transitions under different conditions. The unique features of 2′F-modified DNA should thus be a valuable addition to existing techniques for specific detection of new Z-binding proteins and ligands.

中文翻译：

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C2'-氟化核酸在生理盐条件下形成左手螺旋


细胞生物学的最新发现重新激起了人们对 Z-DNA（DNA 的左手螺旋形式）的兴趣。我们在这里报道了两种最小修饰的核苷，2'F-araC 和 2'F-riboG，在低离子强度下诱导 Z 型的形成。我们证明，完全由这两种核苷组成的寡聚物专门产生与 ADAR1 的 Zα 结构域结合的左手双链体。这两种核苷酸的作用非常显着，以至于 Z 型双链体是在 10 mM 磷酸钠缓冲液和中性 pH 条件下观察到的唯一物种，并且在任何温度下都没有观察到 B 型。因此，与其他报告通过顺式中嘌呤糖苷角的偏好形成 Z/B 形式平衡的研究相比，我们的 NMR 和计算工作表明，连续的 2'F…H2N 和分子内 3'H…N3' 相互作用稳定了左手螺旋。 B-和Z-构象之间的平衡在19F NMR时间尺度（≥ms）内​​是缓慢的，并且每种构象在19F信号中表现出前所未有的化学位移差异。这一观察结果对 B 和 Z 物种的相对种群进行了可靠的估计，并使我们能够监测不同条件下的 B-Z 转变。因此，2'F 修饰 DNA 的独特特征应该是对现有技术的有价值的补充，用于特异性检测新的 Z 结合蛋白和配体。