Synthesis and properties of 4'-C-aminoalkyl-2'-fluoro-modified RNA oligomers.
Bioorg Med Chem
; 26(15): 4574-4582, 2018 08 15.
Article
em En
| MEDLINE
| ID: mdl-30097362
ABSTRACT
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 1â¯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 48â¯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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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
RNA de Cadeia Dupla
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RNA Interferente Pequeno
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Flúor
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article