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.