2′-Fluorination of Tricyclo-DNA Controls Furanose Conformation and Increases RNA Affinity

The
synthesis of 2′-fluoro tricyclo-DNA pyrimidine nucleosides
with fluorine in the ribo-configuration and their incorporation into
oligodeoxynucleotides was accomplished. Unlike the parent tc-T nucleoside,
the 2′F-RNA-tc-T unit occurs in the 2′-exo conformation
in the crystal. Specifically, F-RNA-tc-T was found to stabilize duplexes
with RNA by +2 to +4 °C in Tm/mod.
F-RNA-tc-nucleosides mix well with the DNA backbone and thus open
up possibilities of using shorter and mixed-(DNA/tc-DNA) backbone
oligonucleotides for therapeutic applications.