2′-Fluoro Substituents Can Mimic Native 2′-Hydroxyls within Structured RNA

SummaryThe ability of fluorine in a C-F bond to act as a hydrogen bond acceptor is controversial. To test such ability in complex RNA macromolecules, we have replaced native 2′-OH groups with 2′-F and 2′-H groups in two related systems, the Tetrahymena group I ribozyme and the ΔC209 P4-P6 RNA domain. In three cases the introduced 2′-F mimics the native 2′-OH group, suggesting that the fluorine atom can accept a hydrogen bond. In each of these cases the native hydroxyl group interacts with a purine exocyclic amine. Our results give insight about the properties of organofluorine and suggest a possible general biochemical signature for tertiary interactions between 2′-hydroxyl groups and exocyclic amino groups within RNA.

Graphical AbstractFigure optionsDownload high-quality image (70 K)Download as PowerPoint slideHighlights
► We tested the ability of organofluorine to accept hydrogen bonds in two RNA systems
► In three cases a 2′-F, but not a 2′-H, can effectively substitute the native 2′-OH
► In these cases the native 2′-OH accepts a hydrogen bond from a purine amino group
► We suggest that a 2′-F can accept a hydrogen bond from an RNA purine amino group