siRNAs against luciferase mRNA were modified with amide-linked oligoribonucleosides (amide-linked RNA) at their 3 '-overhangs. Tm values of the modified siRNAs increased compared with that of the unmodified siRNA. These results indicate that the modified overhangs increase the thermodynamic stability of the siRNAs. The modified overhangs improved stability of siRNAs against degradation by nuclease S1 and 50% mouse plasma. Furthermore the modified siRNAs reduced the target gene expression in a similar manner to the unmodified siRNA in cultured cells. These results suggest that the overhang modifications are tolerated for the siRNA activity.
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http://dx.doi.org/10.1080/15257770701542389 | DOI Listing |
Nucleosides Nucleotides Nucleic Acids
March 2008
Department of Biosciences, Teikyo University of Science and Technology, 2525 Yatsusawa, Uenohara, Yamanashi 409-0193, Japan.
siRNAs against luciferase mRNA were modified with amide-linked oligoribonucleosides (amide-linked RNA) at their 3 '-overhangs. Tm values of the modified siRNAs increased compared with that of the unmodified siRNA. These results indicate that the modified overhangs increase the thermodynamic stability of the siRNAs.
View Article and Find Full Text PDFNucleic Acids Symp Ser (Oxf)
August 2007
Department of Biosciences, Teikyo University of Science and Technology, 2525 Yatsusawa, Uenohara, Yamanashi 409-0193, Japan.
siRNAs against luciferase gene were modified with amide-linked oligoribonucleosides (amide-linked RNA) at their 3'-overhang regions. The modified siRNAs were more stable than the unmodified siRNA against degradation by nuclease S1, which indicates that the modified overhang regions increase the nuclease resistance of the siRNAs. Tm values of the modified siRNAs increased compared with that of the unmodified siRNA.
View Article and Find Full Text PDFJ Org Chem
May 2000
Department of Chemistry, Brigham Young University, Provo, Utah 84602-5700, USA.
Treatment of a 1,2-O-isopropylidene-3-ketopentofuranose derivative (obtained from D-glucose) with [(ethoxycarbonyl)methylene]triphenylphosphorane and catalytic hydrogenation of the resulting alkene gave stereodefined access to 3-(carboxymethyl)-3-deoxy-D-ribofuranose derivatives. Esters of 5-O-acetyl- or 5-azido-5-deoxy-3-(carboxymethyl)-D-ribofuranose were coupled with nucleobases to give branched-chain nucleoside derivatives. Ester saponification and protecting group manipulation provided 2'-O-(tert-butyldimethylsilyl) ethers of 5'-azido-5'-deoxy- or 5'-O-(dimethoxytrityl) derivatives of 3'-(carboxymethyl)-3'-deoxyribonucleosides that are effective precursors for synthesis of amide-linked oligoribonucleosides.
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