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Title

Conformationally rigid nucleoside probes help understand the role of sugar pucker and nucleobase orientation in the thrombin-binding aptamer

AuthorsSaneyoshi, Hisao; Mazzini, Stefania; Aviñó, Anna CSIC ORCID; Portella, Guillem; González, Carlos CSIC ; Orozco, Modesto; Márquez, Víctor E.; Eritja Casadellà, Ramón CSIC ORCID
KeywordsThrombin-Binding Aptamer (TBA)
NMR spectra
Issue Date20-Jul-2009
PublisherOxford University Press
CitationNucleic Acids Research 37(17): 5589–5601 (2009)
AbstractModified thrombin-binding aptamers carrying 2′-deoxyguanine (dG) residues with locked North- or South-bicyclo[3.1.0]hexane pseudosugars were synthesized. Individual 2′-deoxyguanosines at positions dG5, dG10, dG14 and dG15 of the aptamer were replaced by these analogues where the North/anti and South/syn conformational states were confined. It was found that the global structure of the DNA aptamer was, for the most part, very accommodating. The substitution at positions 5, 10 and 14 with a locked South/syn-dG nucleoside produced aptamers with the same stability and global structure as the innate, unmodified one. Replacing position 15 with the same South/syn-dG nucleoside induced a strong destabilization of the aptamer, while the antipodal North/anti-dG nucleoside was less destabilizing. Remarkably, the insertion of a North/anti-dG nucleoside at position 14, where both pseudosugar conformation and glycosyl torsion angle are opposite with respect to the native structure, led to the complete disruption of the G-tetraplex structure as detected by NMR and confirmed by extensive molecular dynamics simulations. We conclude that conformationally locked bicyclo[3.1.0]hexane nucleosides appear to be excellent tools for studying the role of key conformational parameters that are critical for the formation of a stable, antiparallel G-tetrad DNA structures.
Description13 pages, 8 figures, 2 tables.-- PMID: 19620215 [PubMed].-- PMCID: PMC2761269.-- Printed version published Sep 2009.
Publisher version (URL)http://dx.doi.org/10.1093/nar/gkp598
URIhttp://hdl.handle.net/10261/25193
DOI10.1093/nar/gkp598
ISSN0305-1048
E-ISSN1362-4962
Appears in Collections:(IQAC) Artículos

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