The use of conformationally rigid nucleoside probes to study the role of sugar pucker and nucleobase orientation in the thrombin binding aptamer.
|The use of conformationally rigid nucleoside probes to study the role of sugar pucker and nucleobase orientation in the thrombin binding aptamer.
|Year of Publication
|Saneyoshi, Hisao, Mazzini Stefania, Aviñó Anna, Portella Guillem, González Carlos, Orozco Modesto, Marquez Victor E., and Eritja Ramon
|Nucleic Acids Symp Ser (Oxf)
|Aptamers, Deoxyguanosine, Hexanes, Nucleic Acid Conformation, Nucleosides, Nucleotide
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.