The effect on quadruplex stability of North-nucleoside derivatives in the loops of the thrombin-binding aptamer.
Modified thrombin-binding aptamers (TBAs) carrying uridine (U), 2'-deoxy-2'-fluorouridine (FU) and North-methanocarbathymidine (NT) residues in the loop regions were synthesized and analyzed by UV thermal denaturation experiments and CD spectroscopy. The replacement of thymidines in the TGT loop by U and FU results in an increased stability of the antiparallel quadruplex structure described for the TBA while the presence of NT residues in the same positions destabilizes the antiparallel structure. The substitution of the thymidines in the TT loops for U, FU and NT induce a destabilization of the antiparallel quadruplex, indicating the crucial role of these positions. NMR studies on TBAs modified with uridines at the TGT loop also confirm the presence of the antiparallel quadruplex structure. Nevertheless, replacement of two Ts in the TT loops by uridine gives a more complex scenario in which the antiparallel quadruplex structure is present along with other partially unfolded species or aggregates.
Institute for Research in Biomedicine (IRB Barcelona), Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and Institute for Advanced Chemistry of Catalonia (IQAC), CSIC, Baldiri Reixac 10, E-08028 Barcelona, Spain. aaagma@cid.csic.es
Anna
A
Aviñó
Stefania
S
Mazzini
Ruben
R
Ferreira
Raimundo
R
Gargallo
Victor E
VE
Marquez
Ramon
R
Eritja
D052157:Aptamers, Nucleotide / Q000737:chemistry*; D002942:Circular Dichroism; D003856:Deoxyuracil Nucleotides / Q000737:chemistry; D054856:G-Quadruplexes; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009705:Nucleosides / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics; D013936:Thymidine / Q000031:analogs & derivatives / Q000737:chemistry; D014466:Ultraviolet Rays; D014529:Uridine / Q000737:chemistry
D052157:Aptamers, Nucleotide; D003856:Deoxyuracil Nucleotides; D009705:Nucleosides; C063781:carbathymidine; C081676:thrombin aptamer; C019324:2'-deoxy-2'-fluorouridine-5'-triphosphate; D013936:Thymidine; D014529:Uridine