Structural Comparison of Oligoribonucleotides and Their 2prime-Deoxy-2prime-fluoro Analogs by heteronuclear NMR spectroscopy

1-(2prime-Deoxy-2prime-fluororibofuranosyl)pyrimidines were synthesized and incorporated into an RNA oligonucleotide to give 5prime-r[CfGCf(UfUfCfG)GCfG]-3prime (Cf: short form of Cd2primef2prime = 2prime-deoxy-2prime-fluorocytidine; Uf: short form of Ud2primef2prime = 2prime-deoxy-2prime-fluorouridine). The oligomer was investigated by means of UV, CD, and NMR spectroscopy to address the question of how F-labels can substitute 13C-labels in the ribose ring. Through-space (NOE) and through-bond (scalar couplings) experiments were performed that make use of the ameliorated chemical-shift dispersion induced by 19F as an alternative heteronucleus. A comparison of the structures of fluorinated vs. unmodified oligomer is given. It turns out that the fluorinated oligonucleotide exists in a 14:3 equilibrium between a hairpin and a duplex conformation, in contrast to the unmodified oligonucleotide which predominantly adopts the hairpin conformation. Furthermore, the fluorinated hairpin structure adopts two distinct conformations that differ in the sugar conformation of the Uf5 and Cf6 nucleoside units, as detected by the 19F-NMR chemical shifts. The role of the 2prime-OH group as stabilizing element in RNA secondary structure is discussed.