7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove

José M. Ibarra-Soza, Alexi A. Morris, Prasanna Jayalath, Hayden Peacock, Wayne E. Conrad, Michael B. Donald, Mark J. Kurth, Peter A. Beal

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Here we describe the synthesis of new 7-substituted 8-aza-7-deazaadenosine ribonucleoside phosphoramidites and their use in generating major groove-modified duplex RNAs. A 7-ethynyl analog leads to further structural diversification of the RNA via post-automated RNA synthesis azide-alkyne cycloaddition reactions. In addition, we report preliminary studies on the effects of eight different purine 7-position modifications on RNA duplex stability and pairing specificity. Finally, the effect on RNAi activity of this type of modification at eight different positions in an siRNA guide strand has been explored. Analogs were identified with large 7-position substituents that maintain adenosine pairing specificity and are well-tolerated at specific positions in an siRNA guide strand. This journal is

Original languageEnglish (US)
Pages (from-to)6491-6497
Number of pages7
JournalOrganic and Biomolecular Chemistry
Volume10
Issue number32
DOIs
StatePublished - Aug 28 2012

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grooves
Small Interfering RNA
RNA
strands
Ribonucleosides
Alkynes
Azides
RNA Stability
Cycloaddition Reaction
analogs
RNA Interference
adenosines
Adenosine
purines
Cycloaddition
cycloaddition
alkynes
synthesis
4-aminopyrazolopyrimidine-2'-deoxyribofuranoside
phosphoramidite

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

Cite this

Ibarra-Soza, J. M., Morris, A. A., Jayalath, P., Peacock, H., Conrad, W. E., Donald, M. B., ... Beal, P. A. (2012). 7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove. Organic and Biomolecular Chemistry, 10(32), 6491-6497. https://doi.org/10.1039/c2ob25647a

7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove. / Ibarra-Soza, José M.; Morris, Alexi A.; Jayalath, Prasanna; Peacock, Hayden; Conrad, Wayne E.; Donald, Michael B.; Kurth, Mark J.; Beal, Peter A.

In: Organic and Biomolecular Chemistry, Vol. 10, No. 32, 28.08.2012, p. 6491-6497.

Research output: Contribution to journalArticle

Ibarra-Soza, JM, Morris, AA, Jayalath, P, Peacock, H, Conrad, WE, Donald, MB, Kurth, MJ & Beal, PA 2012, '7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove', Organic and Biomolecular Chemistry, vol. 10, no. 32, pp. 6491-6497. https://doi.org/10.1039/c2ob25647a
Ibarra-Soza JM, Morris AA, Jayalath P, Peacock H, Conrad WE, Donald MB et al. 7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove. Organic and Biomolecular Chemistry. 2012 Aug 28;10(32):6491-6497. https://doi.org/10.1039/c2ob25647a
Ibarra-Soza, José M. ; Morris, Alexi A. ; Jayalath, Prasanna ; Peacock, Hayden ; Conrad, Wayne E. ; Donald, Michael B. ; Kurth, Mark J. ; Beal, Peter A. / 7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove. In: Organic and Biomolecular Chemistry. 2012 ; Vol. 10, No. 32. pp. 6491-6497.
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