The use of conformationally rigid nucleoside probes to study the role of sugar pucker and nucleobase orientation in the thrombin binding aptamer.

TitleThe use of conformationally rigid nucleoside probes to study the role of sugar pucker and nucleobase orientation in the thrombin binding aptamer.
Publication TypeJournal Article
Year of Publication2009
AuthorsSaneyoshi, Hisao, Mazzini Stefania, Aviñó Anna, Portella Guillem, González Carlos, Orozco Modesto, Marquez Victor E., and Eritja Ramon
JournalNucleic Acids Symp Ser (Oxf)
Pagination109-10
Date Published2009
ISSN1746-8272
KeywordsAptamers, Deoxyguanosine, Hexanes, Nucleic Acid Conformation, Nucleosides, Nucleotide
Abstract

Thrombin 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.

DOI10.1093/nass/nrp055