Synthesis and properties of 4′-C-aminoalkyl-2′-fluoro-modified RNA oligomers

Add time:08/18/2019    Source:sciencedirect.com

Synthesis and properties of double-stranded RNAs (dsRNAs) and small interfering RNAs (siRNAs) containing 4′-C-aminoethyl-2′-deoxy-2′-fluorouridine are described. Thermal denaturation studies showed that incorporation of 4′-C-aminoethyl-2′-fluoro analog improved the thermal stabilities of dsRNAs and siRNAs compared to the corresponding 4′-C-aminoethyl-2′-O-methyl analog. siRNA incorporating eight 4′-aminoethyl-2′-fluoro analogs in the passenger strand showed sufficient RNAi activity at 1 nM concentration, which was similar to that of the unmodified siRNA. Furthermore, the siRNA containing the 4′-C-aminoethyl-2′-fluoro analog exhibited high stability in a buffer containing 20% bovine serum. Forty-eight percent of the siRNA remained intact after 48 h of incubation. Thus, modification of siRNAs by the 4′-C-aminoethyl-2′-fluoro analog would be useful for the development of therapeutic siRNA molecules.

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