Synthesis and Structure of 4'-CF3-Uridine Modified Oligoribonucleotides

The synthesis and structure of 4'-CF3-uridine modified ribonucleotides are reported. Active 4'-CF3-uridine (U4'-TfM) phosphoramidite was prepared and successfully incorporated into oligonucleotides based on solid-supported synthesis. Molecular dynamics simulations and NMR studies of the U4'-TfM modified oligonucleotides revealed that the ribose of U4'-TfM was constrained in the South conformation, which was corroborated by the biochemical properties of the U4'-TfM modified oligonucleotide, such as their affinity to complementary strands and transesterification kinetics. The South-constrained conformation, together with the intense F-19 NMR signal of the U4'-TfM makes it an ideal probe for studying the structure and function of RNA.