19F-Site-Specific-Labeled Nucleotides for Nucleic Acid Structural Analysis by NMR

2′-O-Trifluoromethylated RNA – a powerful modification for RNA chemistry and NMR spectroscopy

“…This nding is consistent with a preferential C3 0 -endo conformation of the 2 0 -OCF 3 ribose in short single stranded RNA as shown by measurements and interpretation of H1 0 -H2 0 coupling constants. Moreover, we demonstrate the exceptionally high sensitivity of the new label in 19 F-NMR analysis of RNA structure equilibria and of RNA-small molecule interactions. The study is complemented by crystal structures of an RNA hairpin including 2 0 -OCF 3 modications.…”

“…1A ‡). The very same hairpin was also used to demonstrate the impressive 19 F NMR spectroscopic sensitivity of the 2 0 -OCF 3 label compared to a 2 0 -F label (ESI Fig. 1B and C ‡).…”

“…The attractiveness of uorine labeling of biomolecules for 19 F-NMR spectroscopic applications originates from its unique properties, namely a 100% natural abundance, high NMR sensitivity, and large chemical shi dispersion. [1][2][3][4][5][6][7][8][9] Moreover, uorine is bio-orthogonal, meaning that it is hardly encountered in native biomolecular systems.…”

“…[1][2][3][4][5][6][7][8][9] Moreover, uorine is bio-orthogonal, meaning that it is hardly encountered in native biomolecular systems. [10][11][12][13][14][15] Appropriate probes for ribonucleic acids have mainly focused on single uorine atoms attached to the 5-position of pyrimidine nucleobases [16][17][18][19][20] or at the ribose 2 0 -position. [21][22][23][24][25] To further increase sensitivity, tri-uoromethyl labeling approaches have been sought aer, 26,27 one of them focuses on ribose 2 0 -triuoromethylthio (2 0 -SCF 3 ) modi-cations.…”

“…To the best of our knowledge, only one study is available that describes the thermodynamic stabilities of a short DNA containing a single 2 0 -OCF 3 group that is paired to either a complementary DNA or RNA strand. 31 We expected the 2 0 -OCF 3 modication highly benecial for RNA and 19 F-NMR spectroscopic applications to analyze structural dynamics and ligand interactions, and therefore, we set out to overcome the underlying challenges in chemical synthesis. In this work, we present synthetic routes toward 2 0 -OCF 3 nucleoside phosphoramidites and their incorporation into oligoribonucleotides by RNA solidphase synthesis.…”