Sulfonylation of RNA 2'-OH groups.

Area of Science:

• Chemical Biology
• Nucleic Acid Chemistry
• Bioconjugation

Background:

• RNA 2 ahydroxyl (2 ahydroxyl) groups are reactive nucleophiles in aqueous environments.
• Existing methods for selective RNA 2 ahydroxyl modification often rely on unstable carbonyl electrophiles.

Purpose of the Study:

• To develop novel reagents for selective RNA 2 ahydroxyl modification with improved stability and versatility in water.
• To explore the utility of these reagents for RNA labeling, conjugation, and structural analysis.

Main Methods:

• Synthesis and characterization of activated small-molecule sulfonyl species, particularly aryl sulfonyltriazoles.
• Evaluation of reagent stability, aqueous solubility, and reactivity with RNA.
• Application of sulfonyl reagents for RNA labeling (including click chemistry) and structure probing.

Main Results:

• Activated sulfonyl species exhibit extended lifetimes and favorable aqueous solubility, enabling efficient RNA-selective reactions.
• Aryl sulfonyltriazoles are more stable than previous electrophiles and tolerate silica chromatography.
• An azide-substituted reagent facilitates RNA labeling via click chemistry.
• RNA sulfonylation shows selectivity for unpaired nucleotides and can be used for structure mapping.
• Demonstrated cell permeability and probing of rRNA in human cells.

Conclusions:

• The developed sulfonyl reagent class provides a new platform for controlled, selective, and versatile RNA modification in aqueous solution.
• These reagents offer advantages in ease of preparation and application for diverse RNA research, including in cellular contexts.