Issue 32, 2012
From the journal:

Organic & Biomolecular Chemistry

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

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

* Corresponding authors

a Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616, USA
E-mail: info@chem.ucdavis.edu
Fax: +1 (530) 752-8995
Tel: +1 (530) 752-8900

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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Article information

DOI
https://doi.org/10.1039/C2OB25647A
Article type
Paper
Submitted
31 Mar 2012
Accepted
19 Jun 2012
First published
19 Jun 2012

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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