Hexofuranosyl thymidines inserted into oligodeoxynucleotides via their two exocyclic hydroxy groups. Oligo synthesis and RNase H activity Original Research Article

Hexofuranosyl nucleosides are considered as conformationally restricted acyclic nucleosides using a furanose ring to link the diol backbone to the nucleobase. The phosphoramidite of 1-(2,3-dideoxy-β-d-erythro-hexofuranosyl)thymine was synthesized from thymidine with formation of a new stereocentre at C-5′ and the nucleoside was used in oligodeoxynucleotide (ODN) synthesis. Binding of mixed sequence ODNs towards complementary DNA and RNA showed decreased affinity compared to the wild-type oligos. Insertion in the middle of poly αT sequence led to stabilization of ODN/dA14 duplexes at low ionic strength, but a decrease was observed in medium and high salt buffers compared to d(αT)14/dA14. Both β and α hexofuranosyl thymidines allowed cleavage of complementary mixed-sequence RNA by RNase H to the 3′-site of the modification in ODNs whereas a limited inhibition was detected from the 5′-site.