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Differential stability of 2′F-ANA•RNA and ANA•RNA hybrid duplexes: Roles of structure, pseudohydrogen bonding, hydration, ion uptake and flexibility

AuthorsWatts, Johnathan K.; Martín-Pintado, N. CSIC; Gómez-Pinto, Irene; Schwartzentruber, Jeremy; Portella, Guillem; Orozco, Modesto; González, Carlos CSIC ; Damha, M.J.
Issue Date13-Jan-2010
PublisherOxford University Press
CitationNucleic Acids Research 38: 2498-2511 (2010)
AbstractHybrids of RNA with arabinonucleic acids 2′F-ANA and ANA have very similar structures but strikingly different thermal stabilities. We now present a thorough study combining NMR and other biophysical methods together with state-of-the-art theoretical calculations on a fully modified 10-mer hybrid duplex. Comparison between the solution structure of 2′F-ANA•RNA and ANA•RNA hybrids indicates that the increased binding affinity of 2′F-ANA is related to several subtle differences, most importantly a favorable pseudohydrogen bond (2′F-purine H8) which contrasts with unfavorable 2′-OH-nucleobase steric interactions in the case of ANA. While both 2′F-ANA and ANA strands maintained conformations in the southern/eastern sugar pucker range, the 2′F-ANA strand's structure was more compatible with the A-like structure of a hybrid duplex. No dramatic differences are found in terms of relative hydration for the two hybrids, but the ANA•RNA duplex showed lower uptake of counterions than its 2′F-ANA•RNA counterpart. Finally, while the two hybrid duplexes are of similar rigidities, 2′F-ANA single strands may be more suitably preorganized for duplex formation. Thus the dramatically increased stability of 2′F-ANA•RNA and ANA•RNA duplexes is caused by differencesin at least four areas, of which structure and pseudohydrogen bonding are the most important. © The Author(s) 2010. Published by Oxford University Press.
Description14 pags., 7 figs., 3 tabs.
Publisher version (URL)http://dx.doi.org/10.1093/nar/gkp1225
Identifiersdoi: 10.1093/nar/gkp1225
issn: 0305-1048
Appears in Collections:(IQFR) Artículos
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