English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/167827
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


Rigid 2′,4′-difluororibonucleosides: Synthesis, conformational analysis, and incorporation into nascent RNA by HCV polymerase

AuthorsMartínez-Montero, S.; Deleavey, G.F.; Kulkarni, A.; Martín-Pintado, N. ; Lindovska, P.; Thomson, M.; González, Carlos ; Götte, M.; Damha, M.J.
Issue Date2014
PublisherAmerican Chemical Society
CitationJournal of Organic Chemistry 79: 5627- 5635 (2014)
AbstractWe report on the synthesis and conformational properties of 2′-deoxy-2′,4′-difluorouridine (2′,4′-diF-rU) and cytidine (2′,4′-diF-rC) nucleosides. NMR analysis and quantum mechanical calculations show that the strong stereoelectronic effects induced by the two fluorines essentially ́locḱ the conformation of the sugar in the North region of the pseudorotational cycle. Our studies also demonstrate that NS5B HCV RNA polymerase was able to accommodate 2′,4′-diF-rU 5′-triphosphate (2′,4′-diF-rUTP) and to link the monophosphate to the RNA primer strand. 2′,4′-diF-rUTP inhibited RNA synthesis in dinucleotide-primed reactions, although with relatively high half-maximal inhibitory concentrations (IC50 > 50 μM). 2′,4′- diF-rU/C represents rare examples of ́locked́ ribonucleoside mimics that lack a bicyclic ring structure. © 2014 American Chemical Society.
Identifiersdoi: 10.1021/jo500794v
issn: 1520-6904
Appears in Collections:(IQFR) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.