Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/129851
Title: | Synthesis and Properties of 2′-Deoxy-2′,4′-difluoroarabinose-Modified Nucleic Acids |
Author: | Martínez-Montero, Saúl Deleavey, Glen F. Dierker-Viil, Arden Lindovska, Petra Ilina, Tatiana Portella, Guillem Orozco López, Modesto Parniak, Michael A. Damha, Masad J. |
Keywords: | Síntesi de l'ADN Química orgànica DNA synthesis Organic chemistry |
Issue Date: | 27-Feb-2015 |
Publisher: | American Chemical Society |
Abstract: | We 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). |
Note: | Versió postprint del document publicat a: https://doi.org/10.1021/jo502948t |
It is part of: | Journal of Organic Chemistry, 2015, vol. 80, num. 6, p. 3083-3091 |
URI: | http://hdl.handle.net/2445/129851 |
Related resource: | https://doi.org/10.1021/jo502948t |
ISSN: | 0022-3263 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
652658.pdf | 1.13 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.