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The use of conformationally rigid nucleoside probes to study 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
Issue Date27-Sep-2009
PublisherOxford University Press
CitationNucleic Acids Symposium Series 53(1): 109-110 (2009)
AbstractThrombin binding aptamers (TBAs) incorporating North-/South-deoxyguanosines built on the rigid bicyclo[3.1.0]hexane template were synthesized. Individual 2'-deoxyguanosines at positions dG14 and dG15 of the aptamer were replaced by these analogues where the North/anti and South/syn conformational states were confined. The substitution at position 14 with a locked South/syn-dG nucleoside produced an aptamer with the same stability and global structure as the innate, unmodified one. Replacing position 15 with the same South/syndG 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.
Description2 pages, 1 figure, 1 table.-- PMID: 19749284 [PubMed].
Publisher version (URL)http://dx.doi.org/10.1093/nass/nrp055
ISSN1746-8272 (Online)
Appears in Collections:(IQAC) Artículos
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