Synthesis and characterization of 4′-C-guanidinomethyl-2′-O-methyl-modified RNA oligomers.

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. [ABSTRACT FROM AUTHOR]