4′-SCF3-Labeling Constitutes a Sensitive 19F NMR Probe for Characterization of Interactions in the Minor Groove of DNA

Fluorinated nucleotides are invaluable for F-19 NMR studies of nucleic acid structure and function. Here, we synthesized 4 '-SCF3-thymidine (T 4'-SCF3 ${{<^>{4{<^>\prime}\hbox{-}{\rm SCF}{_{3}}}}}$ ) and incorporated it into DNA by means of solid-phase DNA synthesis. NMR studies showed that the 4 '-SCF3 group exhibited a flexible orientation in the minor groove of DNA duplexes and was well accommodated by various higher order DNA structures. The three magnetically equivalent fluorine atoms in 4 '-SCF3-DNA constitute an isolated spin system, offering high F-19 NMR sensitivity and excellent resolution of the positioning of T 4'-SCF3 ${{<^>{4{<^>\prime}\hbox{-}{\rm SCF}{_{3}}}}}$ within various secondary and tertiary DNA structures. The high structural adaptability and high sensitivity of T 4'-SCF3 ${{<^>{4{<^>\prime}\hbox{-}{\rm SCF}{_{3}}}}}$ make it a valuable F-19 NMR probe for quantitatively distinguishing diverse DNA structures with single-nucleotide resolution and for monitoring the dynamics of interactions in the minor groove of double-stranded DNA.

Automated summary

Fluorinated nucleotides are crucial for F-19 NMR studies of nucleic acid structure and function. The synthesized 4'-SCF3-thymidine exhibits high adaptability and sensitivity, making it valuable for distinguishing diverse DNA structures with single-nucleotide resolution.