Martínez-Montero, SaúlDeleavey, Glen F.Dierker-Viil, ArdenLindovska, PetraIlina, TatianaPortella, GuillemOrozco López, ModestoParniak, Michael A.Damha, Masad J.2019-03-062019-03-062015-02-270022-3263https://hdl.handle.net/2445/129851We report the synthesis, thermal stability, and RNase H substrate activity of 2′-deoxy-2′,4′-difluoroarabino-modified nucleic acids. 2′-Deoxy-2′,4′-difluoroarabinouridine (2,′4′-diF-araU) was prepared in a stereoselective way in six steps from 2′-deoxy-2′-fluoroarabinouridine (2′-F-araU). NMR analysis and quantum mechanical calculations at the nucleoside level reveal that introduction of 4′-fluorine introduces a strong bias toward the North conformation, despite the presence of the 2′-βF, which generally steers the sugar pucker toward the South/East conformation. Incorporation of the novel monomer into DNA results on a neutral to slightly stabilizing thermal effect on DNA-RNA hybrids. Insertion of 2′,4′-diF-araU nucleotides in the DNA strand of a DNA-RNA hybrid decreases the rate of both human and HIV reverse transcriptase-associated RNase H-mediated cleavage of the complement RNA strand compared to that for an all-DNA strand or a DNA strand containing the corresponding 2′-F-araU nucleotide units, consistent with the notion that a 4′-fluorine in 2′-F-araU switches the preferred sugar conformation from DNA-like (South/East) to RNA-like (North).9 p.application/pdfeng(c) American Chemical Society , 2015Síntesi de l'ADNQuímica orgànicaDNA synthesisOrganic chemistryinfo:eu-repo/semantics/article6526582019-03-06info:eu-repo/semantics/openAccess25723361