Back to Search
Start Over
Influence of 2′-Modifications (O-Methylation, Fluorination, and Stereochemical Inversion) on the Base Pairing Energies of Protonated Cytidine Nucleoside Analogue Base Pairs: Implications for the Stabilities of i‑Motif Structures.
- Source :
-
Journal of the American Society for Mass Spectrometry . 7/5/2023, Vol. 34 Issue 7, p1400-1416. 17p. - Publication Year :
- 2023
-
Abstract
- Naturally occurring and chemically engineered modifications are among the most powerful strategies explored for fine-tuning the conformational characteristics and intrinsic stability of nucleic acids topologies. Modifications at the 2′-position of the ribose or 2′-deoxyribose moieties differentiate nucleic acid structures and have a significant impact on their electronic properties and base-pairing interactions. 2′-O-Methylation, a common post-transcriptional modification of tRNA, is directly involved in modulating specific anticodon–codon base-pairing interactions. 2′-Fluorinated and arabino nucleosides possess novel and beneficial medicinal properties and find use as therapeutics for treating viral diseases and cancer. However, the potential to deploy 2′-modified cytidine chemistries for tuning i-motif stability is largely unknown. To address this knowledge gap, the effects of 2′-modifications including O-methylation, fluorination, and stereochemical inversion on the base-pairing interactions of protonated cytidine nucleoside analogue base pairs, the core stabilizing interactions of i-motif structures, are examined using complementary threshold collision-induced dissociation techniques and computational methods. The 2′-modified cytidine nucleoside analogues investigated here include 2′-O-methylcytidine, 2′-fluoro-2′-deoxycytidine, arabinofuranosylcytosine, 2′-fluoro-arabinofuranosylcytosine, and 2′,2′-difluoro-2′-deoxycytidine. All five 2′-modifications examined here are found to enhance the base-pairing interactions relative to the canonical DNA and RNA cytidine nucleosides with the greatest enhancements arising from 2′-O-methylation and 2′,2′-difluorination, suggesting that these modifications should well be tolerated in the narrow grooves of i-motif conformations. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10440305
- Volume :
- 34
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Journal of the American Society for Mass Spectrometry
- Publication Type :
- Academic Journal
- Accession number :
- 164761240
- Full Text :
- https://doi.org/10.1021/jasms.3c00108