Structural and Energetic Effects of O2′-Ribose Methylation of Protonated Purine Nucleosides

• DOI: 10.1021/acs.jpcb.8b07687
• Publication Date: 2018-09-11T09:32:11Z
• Authors: C. C. He; L. A. Hamlow; Zachary J. Devereaux; Y. Zhu; Y.-w. Nei; L. Fan; C. P. McNary; P. Maitre; V. Steinmetz; B. Schindler; I. Compagnon; P. B. Armentrout; M. T. Rodgers
• Keywords: Nucleobase; Ribose; Glycosidic bond

The chemical difference between DNA and RNA nucleosides is their 2′-hydrogen versus 2′-hydroxyl substituents. Modification of the ribosyl moiety at 2′-position 2′-O-methylation in particular, common among natural post-transcriptional modifications RNA. 2′-Modification may alter electronic properties hydrogen-bonding characteristics nucleoside thus lead to enhanced stabilization or malfunction. structures relative glycosidic bond stabilities protonated forms 2′-O-methylated purine nucleosides, 2′-O-methyladenosine (Adom) 2′-O-methylguanosine (Guom), were examined using two complementary tandem mass spectrometry approaches, infrared multiple photon dissociation action spectroscopy energy-resolved collision-induced dissociation. Theoretical calculations also performed predict stable low-energy conformations spectra gas phase. Low-energy highly parallel those found for canonical are nucleosides. Importantly, preferred site protonation, nucleobase orientation, sugar puckering preserved DNA, RNA, variants 2′-substituent does however influence hydrogen-bond as 2′-O-methyl substituents enable a interaction 2′- 3′-substituents, whereas atom not. Further, reduces number hydrogen-bonded possible importantly inverts polarity this that analogues. Trends CID50% values extracted from survival yield analyses employed elucidate stabilities. stability Adom exceed its Guom analogue; however, modification weakens counterpart. appears be correlated with moiety.