8-oxoguanosine switches modulate the activity of alkylated siRNAs by controlling steric effects in the major versus minor grooves

Arunkumar Kannan, Erik Fostvedt, Peter A. Beal, Cynthia J. Burrows

Research output: Contribution to journalArticle

10 Scopus citations


Small interfering double-stranded RNAs have been synthesized bearing one or more base modifications at nucleotide positions 4, 11, and/or 16 in the guide strand. The chemically modified base is an N2-alkyl-8-oxo-7,8- dihydroguanine (alkyl = propyl, benzyl) that can alternatively pair in a Watson-Crick sense opposite cytosine (C) or as a Hoogsteen pair opposite adenine (A). Cellular delivery with C opposite led to effective targeting of A-containing but not C-containing mRNA sequences in a dual luciferase assay with RNA interference levels that were generally as good as or better than unmodified sequences. The higher activity is ascribed to an inhibitory effect of the alkyl group projecting into the minor groove of double-stranded RNA preventing off-target binding to proteins such as PKR (RNA-activated protein kinase).

Original languageEnglish (US)
Pages (from-to)6343-6351
Number of pages9
JournalJournal of the American Chemical Society
Issue number16
StatePublished - Apr 27 2011


ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

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