Structures and Relative Glycosidic Bond Stabilities of Protonated 2′-Fluoro-Substituted Purine Nucleosides
Structures and Relative Glycosidic Bond Stabilities of Protonated 2′-Fluoro-Substituted Purine Nucleosides
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DOI：
10.1007/s13361-019-02222-6
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发表时间：
2019-08-01
影响因子：
3.2
通讯作者：
Rodgers, M. T.
中科院分区：
文献类型：
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作者：
Devereaux, Zachary J.;He, C. C.;Rodgers, M. T.
2-取代基是DNA和RNA核苷之间的主要区别特征。对这个关键位置的修饰，无论是天然存在的还是合成的，都可以产生具有生物学价值的核苷类似物。氟的独特性质使其作为合成核苷修饰特别有趣和医学上有用。在这项工作中，2 '-氟修饰的质子化的气相嘌呤核苷的影响进行了检查，使用互补串联质谱和计算方法。直接比较与以前的研究相关的核苷。红外多光子解离作用光谱在指纹和氢拉伸区域进行允许的实验填充构象的测定。质子化的2 '-氟-2'-脱氧腺苷[Guofl +H]（+）和2 '-氟-2'-脱氧鸟苷[Guofl+H]（+）的填充构象与它们各自的典型DNA和RNA对应物高度平行。N3和N1质子化位点均通过[H +H]（+）接近，分别稳定顺式和反式核碱基取向。在[Guofl+H]（+）中N7质子化和反核碱基取向占主导地位。光谱可观察到的分子内氢键与氟的相互作用，允许更明确的糖puckering测定比可能的典型系统。[Guofl +H]（+）采用C2 '-内切糖起皱，而[Guofl+H]（+）采用C2 '-内切和C3 '-内切糖起皱。能量分辨碰撞诱导解离实验与生存产量分析提供了相对糖苷键的稳定性。质子化的2 '-氟取代嘌呤核苷的N-糖苷键稳定性超过了它们的典型类似物。此外，发现N-糖苷键稳定性随着2 '-取代基的电负性增加而增加，即，H < OH < F。腺嘌呤核苷类似物的N-糖苷键稳定性也大于鸟嘌呤核苷类似物。
The 2-substituent is the primary distinguishing feature between DNA and RNA nucleosides. Modifications to this critical position, both naturally occurring and synthetic, can produce biologically valuable nucleoside analogues. The unique properties of fluorine make it particularly interesting and medically useful as a synthetic nucleoside modification. In this work, the effects of 2 '-fluoro modification on the protonated gas-phase purine nucleosides are examined using complementary tandem mass spectrometry and computational methods. Direct comparisons are made with previous studies on related nucleosides. Infrared multiple photon dissociation action spectroscopy performed in both the fingerprint and hydrogen-stretching regions allows for the determination of the experimentally populated conformations. The populated conformers of protonated 2 '-fluoro-2 '-deoxyadenosine, [Adofl+H](+), and 2 '-fluoro-2 '-deoxyguanosine, [Guofl+H](+), are highly parallel to their respective canonical DNA and RNA counterparts. Both N3 and N1 protonation sites are accessed by [Adofl+H](+), stabilizing syn and anti nucleobase orientations, respectively. N7 protonation and anti nucleobase orientation dominates in [Guofl+H](+). Spectroscopically observable intramolecular hydrogen-bonding interactions with fluorine allow more definitive sugar puckering determinations than possible for the canonical systems. [Adofl+H](+) adopts C2 '-endo sugar puckering, whereas [Guofl+H](+) adopts both C2 '-endo and C3 '-endo sugar puckering. Energy-resolved collision-induced dissociation experiments with survival yield analyses provide relative glycosidic bond stabilities. The N-glycosidic bond stabilities of the protonated 2 '-fluoro-substituted purine nucleosides are found to exceed those of their canonical analogues. Further, the N-glycosidic bond stability is found to increase with increasing electronegativity of the 2 '-substituent, i.e., H < OH < F. The N-glycosidic bond stability is also greater for the adenine nucleoside analogues than the guanine nucleoside analogues.