Synthesis and biological properties of chemically modified siRNAs bearing 1-deoxy-d-ribofuranose in their 3′-overhang region

Article abstract of DOI:10.1016/j.bmcl.2012.01.132

To elucidate the role of the sugar moiety in the two natural nucleotides of the 3′-overhang region of small interfering RNA (siRNA), we synthesized siRNAs that incorporated two abasic nucleosides, 1-deoxy-d-ribofuranose (R ^H). We improved the method for preparing an O-protected abasic nucleoside, 1-deoxy-2,3,5-tri-O-benzoyl-β-d-ribofuranose, via the reductive cleavage of the anomeric position of 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d- ribofuranose. To incorporate R^H into oligonucleotides by the standard phosphoramidite solid phase method, R^H was converted into its phosphoramidite derivative and the solid support linked to a controlled pore glass resin. Chemically modified RNAs possessing R^H at the 3′-overhang region were easily prepared in good yields. siRNAs containing R^H showed moderate nuclease-resistance and a desirable knockdown effect.