title: 7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove.
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.
authors: Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616, USA.
authors: José M
authors: JM
authors: Ibarra-Soza
authors: Alexi A
authors: AA
authors: Morris
authors: Prasanna
authors: P
authors: Jayalath
authors: Hayden
authors: H
authors: Peacock
authors: Wayne E
authors: WE
authors: Conrad
authors: Michael B
authors: MB
authors: Donald
authors: Mark J
authors: MJ
authors: Kurth
authors: Peter A
authors: PA
authors: Beal
mesh_terms: D000241:Adenosine / Q000737:chemistry* / Q000494:pharmacology; D001372:Aza Compounds / Q000737:chemistry* / Q000494:pharmacology; D004355:Drug Stability; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology; D011489:Protein Denaturation; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000187:drug effects; D012263:Ribonucleosides / Q000737:chemistry* / Q000494:pharmacology; D013696:Temperature
chemical_list: D001372:Aza Compounds; D009943:Organophosphorus Compounds; D034741:RNA, Small Interfering; D012263:Ribonucleosides; C434331:phosphoramidite; D000241:Adenosine