This study investigated the synthesis and properties of 4'-C-guanidinomethyl-2'-O-methyluridine and RNAs containing the analog. Thermal and thermodynamic stabilities of double-stranded RNAs (dsRNAs) containing the nucleoside analog were examined. It was found that although the analog decreased the thermal and thermodynamic stabilities of dsRNA, it had base-discrimination ability. The 4'-C-guanidinomethyl modification increased stability of RNAs in a buffer containing serum. Furthermore, small interference RNAs incorporating one analog at the passenger strand still preserved their RNA interference activities. It was suggested that the 4'-guanidinomethyl modification significantly improved cell membrane permeability of RNA. Thus, 4'-C-guanidinomethyl-2'-O-methyl analogs may be useful in improving the properties of therapeutic siRNA molecules.
Keywords: 4′-guanidinomethyl group; RNA interference; cell membrane permeability; nuclease resistance; small interfering RNA; thermal stability.