2'-Fluoro substituents can mimic native 2'-hydroxyls within structured RNA

Area of Science:

• Biochemistry
• RNA molecular biology
• Organofluorine chemistry

Background:

• The role of fluorine in C-F bonds as hydrogen bond acceptors in complex biomolecules like RNA remains debated.
• Understanding these interactions is crucial for RNA structure-function studies and drug design.

Purpose of the Study:

• To investigate the hydrogen bond accepting ability of fluorine in C-F bonds within complex RNA structures.
• To explore the biochemical implications of replacing native 2'-hydroxyl groups with 2'-fluoro groups in RNA.

Main Methods:

• Site-specific replacement of native 2'-hydroxyl (2'-OH) groups with 2'-fluoro (2'-F) and 2'-hydrogen (2'-H) groups.
• Utilized two RNA systems: the Tetrahymena group I ribozyme and the ΔC209 P4-P6 RNA domain.

Main Results:

• In three instances, the introduced 2'-F group effectively mimicked the function of the native 2'-OH group.
• These mimicking interactions involved the fluorine atom accepting a hydrogen bond, typically from a purine exocyclic amine.

Conclusions:

• The study provides evidence that fluorine in a C-F bond can function as a hydrogen bond acceptor in RNA macromolecules.
• These findings offer insights into the properties of organofluorine compounds and suggest a potential biochemical signature for tertiary interactions involving 2'-hydroxyl groups and exocyclic amino groups in RNA.