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siRNA Modified with 2'-Deoxy-2'-C-methylpyrimidine Nucleosides

AuthorsDellafiore, María A.; Aviñó, Anna ; Alagia, Adele ; Montserrat, Javier M.; Iribarren, A. M.; Eritja Casadellà, Ramón
KeywordsDeoxymethylpyrimidine bases
Structure-activity relationships
Issue Date4-Jul-2018
CitationChemBioChem 19 (13):1409-1413 (2018)
Abstract(2'S)-2'-Deoxy-2'-C-methyluridine and (2'R)-2'-deoxy-2'-C-methyluridine were incorporated in the 3'-overhang region of the sense and antisense strands and in positions 2 and 5 of the seed region of siRNA duplexes directed against Renilla luciferase, whereas (2'S)-2'-deoxy-2'-C-methylcytidine was incorporated in the 6-position of the seed region of the same constructions. A dual luciferase reporter assay in transfected HeLa cells was used as a model system to measure the IC50 values of 24 different modified duplexes. The best results were obtained by the substitution of one thymidine unit in the antisense 3'-overhang region by (2'S)- or (2'R)-2'-deoxy-2'-C-methyluridine, reducing IC50 to half of the value observed for the natural control. The selectivity of the modified siRNA was measured, it being found that modifications in positions 5 and 6 of the seed region had a positive effect on the ON/OFF activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publisher version (URL)10.1002/cbic.201800077
Appears in Collections:(IQAC) Artículos
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