RNAi activity of siRNAs modified with 2'-aminoalkyl-substituted fluorinated nucleobases.
We recently reported that a 1'-deoxy-1'-(4,6-difluoro-1H-benzimidazol-1-yl)-2'-(beta-aminoethyl)-beta-d-ribofuranose nucleoside appears to be a universal nucleoside which does not differentiate between the four natural nucleosides A, C, G, and U in duplexes. Moreover, ribozymes modified with this nucleoside analog showed a better or at least equal catalytic activity relative to Watson-Crick mismatches.[1] Due to these data, we investigated the ability of this compound to tolerate Watson-Crick mismatches in order to avoid HIV escape mutations in RNA interference. The influence of this nucleoside analog on siRNA efficiency was analyzed with a proven siRNA targeting GFP.
Haas
Jens
J
Institute for Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Mueller-Kuller
Thea
T
Klein
Stefan
S
Engels
Joachim W
JW
D001483:Base Sequence; D017611:Fluorine Compounds / Q000737:chemistry*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009705:Nucleosides / Q000737:chemistry*; D034622:RNA Interference; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*
D017611:Fluorine Compounds; D009705:Nucleosides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins