Structural and Energetic Effects of O2'-Ribose Methylation of Protonated Pyrimidine Nucleosides

• Published in: Journal of the American Society for Mass Spectrometry Vol. 30; no. 11; p. 2318
• Main Authors: He, C C, Hamlow, L A, Zhu, Y, Nei, Y-W, Fan, L, McNary, C P, Maître, P, Steinmetz, V, Schindler, B, Compagnon, I, Armentrout, P B, Rodgers, M T
• Format: Journal Article
• Language: English
• Published: United States 01.11.2019
• Subjects: Tandem mass spectrometry; Thymine (Thy); Hydrogen-stretching region; Cytosine (Cyt); Nucleoside modification; IR spectrum; Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS); Nucleobase; IR fingerprint region; Density functional theory (DFT); Energy-resolved collision-induced dissociation (ER-CID); 2′-O-methyluridine (Urdm); Simulated annealing; Thymidine (Thd); Nucleoside; Electrospray ionization (ESI); 5-Methyluridine; Glycosidic bond stability; Infrared multiple photon dissociation (IRMPD) action spectroscopy; Quadrupole ion trap mass spectrometer (QIT MS); Cytidine (Cyd); IRMPD spectrum; Uridine (Urd); Gas-phase conformation; 2′-O-methylation; Electronic structure calculations; Nucleobase orientation; Pyrimidine nucleosides; Sugar puckering; Hydrogen-bonding interactions; Protonation; 2′-O-methylcytidine (Cydm); 2′-O-methyl-5-methyluridine (Thdm); Survival yield analysis; Uracil (Ura)
• ISSN: 1879-1123

The 2'-substituents distinguish DNA from RNA nucleosides. 2'-O-methylation occurs naturally in RNA and plays important roles in biological processes. Such 2'-modifications may alter the hydrogen-bonding interactions of the nucleoside and thus may affect the conformations of the nucleoside in an RNA chain. Structures of the protonated 2'-O-methylated pyrimidine nucleosides were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy, assisted by electronic structure calculations. The glycosidic bond stabilities of the protonated 2'-O-methylated pyrimidine nucleosides, [Nuom+H] , were also examined and compared to their DNA and RNA nucleoside analogues via energy-resolved collision-induced dissociation (ER-CID). The preferred sites of protonation of the 2'-O-methylated pyrimidine nucleosides parallel their canonical DNA and RNA nucleoside analogues, [dNuo+H] and [Nuo+H] , yet their nucleobase orientation and sugar puckering differ. The glycosidic bond stabilities of the protonated pyrimidine nucleosides follow the order: [dNuo+H] < [Nuo+H] < [Nuom+H] . The slightly altered structures help explain the stabilization induced by 2'-O-methylation of the pyrimidine nucleosides.