José M Ibarra-Soza

Publications (2)13.6 Total impact

• Article: 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
  [show abstract] [hide abstract]
  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.
  Organic & Biomolecular Chemistry 07/2012; 10(32):6491-7. · 3.70 Impact Factor
• Source

  Available from: Prasanna Jayalath

  Article: Nucleobase and ribose modifications control immunostimulation by a microRNA-122-mimetic RNA.

  Hayden Peacock, Raymond V Fucini, Prasanna Jayalath, José M Ibarra-Soza, Henry J Haringsma, W Michael Flanagan, Aarron Willingham, Peter A Beal
  [show abstract] [hide abstract]
  ABSTRACT: Immune stimulation is a significant hurdle in the development of effective and safe RNA interference therapeutics. Here, we address this problem in the context of a mimic of microRNA-122 by employing novel nucleobase and known 2'-ribose modifications. The nucleobase modifications are analogues of adenosine and guanosine that contain cyclopentyl and propyl minor-groove projections. Via a site-by-site chemical modification analysis, we identify several immunostimulatory 'hot spots' within the miRNA guide strand at which single base modifications significantly reduce immune stimulation. A duplex containing one base modification on each strand proved to be most effective in preventing immune stimulation.
  Journal of the American Chemical Society 06/2011; 133(24):9200-3. · 9.91 Impact Factor