Structural and Energetic Effects of O2'-Ribose Methylation of Protonated Purine Nucleosides.
Structural and Energetic Effects of O2'-Ribose Methylation of Protonated Purine Nucleosides.
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DOI：
10.1021/acs.jpcb.8b07687
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发表时间：
2018-09
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通讯作者：
C. He;L. Hamlow;Zachary J. Devereaux;Yanlong Zhu;Y.-w. Nei;Lin Fan;Christopher P. McNary;Philippe Maître;Vincent Steinmetz;B. Schindler;Isabelle Compagnon;P. Armentrout;M. Rodgers
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文献类型：
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作者：
C. He;L. Hamlow;Zachary J. Devereaux;Yanlong Zhu;Y.-w. Nei;Lin Fan;Christopher P. McNary;Philippe Maître;Vincent Steinmetz;B. Schindler;Isabelle Compagnon;P. Armentrout;M. Rodgers
DNA和RNA核苷之间的化学差异是它们的2 '-氢与2'-羟基取代基。核糖基部分在2 '-位的修饰和特别是2'-O-甲基化在RNA的天然转录后修饰中是常见的。2 '-修饰可改变核苷的电子性质和氢键特征，因此可导致增强的稳定性或故障。采用两种互补的串联质谱方法，红外多光子解离作用光谱和能量分辨碰撞诱导解离，研究了质子化形式的2 '-O-甲基嘌呤核苷，2'-O-甲基腺苷（Adom）和2 '-O-甲基鸟苷（Guom）的结构和相对糖苷键稳定性。理论计算还预测了2 '-O-甲基化嘌呤核苷质子化形式的稳定低能构象的结构和相对稳定性以及它们在气相中的红外光谱。质子化的2 '-O-甲基化嘌呤核苷的低能构象与典型DNA和RNA嘌呤核苷质子化形式的低能构象高度平行。重要的是，质子化、核碱基取向和糖起皱的优选位点在质子化嘌呤核苷的DNA、RNA和2 '-O-甲基化变体中得以保留。然而，2 ′-取代基确实影响氢键稳定，因为2 ′-O-甲基和2 ′-羟基取代基能够在2 ′-和3 ′-取代基之间形成氢键相互作用，而2 ′-氢原子不能。此外，2 '-O-甲基化减少了可能的稳定低能氢键构象的数量，并且重要的是，与RNA类似物相比，反转了这种相互作用的优选极性。从质子化嘌呤核苷的2 ′-O-甲基化和规范DNA和RNA形式的存活产率分析中提取的CID 50%值的趋势用于阐明其相对糖苷键稳定性。发现Adom的糖苷键稳定性超过其DNA和RNA类似物。Guom的糖苷键稳定性也超过其DNA类似物;然而，这种修饰相对于其RNA对应物削弱了这种键。质子化嘌呤核苷的糖苷键稳定性似乎与糖部分的氢键稳定性相关。
The chemical difference between DNA and RNA nucleosides is their 2'-hydrogen versus 2'-hydroxyl substituents. Modification of the ribosyl moiety at the 2'-position and 2'-O-methylation in particular, is common among natural post-transcriptional modifications of RNA. 2'-Modification may alter the electronic properties and hydrogen-bonding characteristics of the nucleoside and thus may lead to enhanced stabilization or malfunction. The structures and relative glycosidic bond stabilities of the protonated forms of the 2'-O-methylated purine nucleosides, 2'-O-methyladenosine (Adom) and 2'-O-methylguanosine (Guom), were examined using two complementary tandem mass spectrometry approaches, infrared multiple photon dissociation action spectroscopy and energy-resolved collision-induced dissociation. Theoretical calculations were also performed to predict the structures and relative stabilities of stable low-energy conformations of the protonated forms of the 2'-O-methylated purine nucleosides and their infrared spectra in the gas phase. Low-energy conformations highly parallel to those found for the protonated forms of the canonical DNA and RNA purine nucleosides are also found for the protonated 2'-O-methylated purine nucleosides. Importantly, the preferred site of protonation, nucleobase orientation, and sugar puckering are preserved among the DNA, RNA, and 2'-O-methylated variants of the protonated purine nucleosides. The 2'-substituent does however influence hydrogen-bond stabilization as the 2'-O-methyl and 2'-hydroxyl substituents enable a hydrogen-bonding interaction between the 2'- and 3'-substituents, whereas a 2'-hydrogen atom does not. Further, 2'-O-methylation reduces the number of stable low-energy hydrogen-bonded conformations possible and importantly inverts the preferred polarity of this interaction versus that of the RNA analogues. Trends in the CID50% values extracted from survival yield analyses of the 2'-O-methylated and canonical DNA and RNA forms of the protonated purine nucleosides are employed to elucidate their relative glycosidic bond stabilities. The glycosidic bond stability of Adom is found to exceed that of its DNA and RNA analogues. The glycosidic bond stability of Guom is also found to exceed that of its DNA analogue; however, this modification weakens this bond relative to its RNA counterpart. The glycosidic bond stability of the protonated purine nucleosides appears to be correlated with the hydrogen-bond stabilization of the sugar moiety.