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Issue 32, 2012
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7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove

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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.

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

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Publication details

The article was received on 31 Mar 2012, accepted on 19 Jun 2012 and first published on 19 Jun 2012


Article type: Paper
DOI: 10.1039/C2OB25647A
Citation: Org. Biomol. Chem., 2012,10, 6491-6497
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    7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove

    J. M. Ibarra-Soza, A. A. Morris, P. Jayalath, H. Peacock, W. E. Conrad, M. B. Donald, M. J. Kurth and P. A. Beal, Org. Biomol. Chem., 2012, 10, 6491
    DOI: 10.1039/C2OB25647A

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