title: Improved thrombin binding aptamer analogues containing inversion of polarity sites: structural effects of extra-residues at the ends.
abstract: In this paper, we report the investigations, based on NMR, molecular modelling, CD measurements and electrophoresis, of thrombin binding aptamer (TBA) analogues containing an extra-residue at the 3'-end or at both the ends of the original TBA sequence, linked through 3'-3' or 5'-5' phosphodiester bonds. The data indicate that most of the modified aptamers investigated adopt chair-like G-quadruplex structures very similar to that of the TBA and that stacking interactions occur between the 3'-3' or 5'-5' extra residues and the deoxyguanosines of the upper G-tetrad. A comparison of the thermodynamic data of TBA-A and TBA-T containing a 3'-3' extra residue and their canonical versions clearly indicates that the 3'-3' phosphodiester bond is fundamental in endowing the modified aptamers with remarkably higher thermal stabilities than the original TBA.
authors.affiliation: Department of Pharmacy, University of Naples Federico II, via D. Montesano, 49, 80131 Naples, Italy. galeone@unina.it verespos@unina.it.
authors.forename: A
authors.initials: A
authors.lastname: Virgilio
authors.affiliation: Department of Pharmacy, University of Naples Federico II, via D. Montesano, 49, 80131 Naples, Italy. galeone@unina.it verespos@unina.it.
authors.forename: T
authors.initials: T
authors.lastname: Amato
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, via Cintia, I-80126 Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Petraccone
authors.affiliation: Department of Experimental Medicine, Second University of Naples, via Costantinopoli 16, 80138 Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Filosa
authors.affiliation: Department of Pharmacy, University of Naples Federico II, via D. Montesano, 49, 80131 Naples, Italy. galeone@unina.it verespos@unina.it.
authors.forename: M
authors.initials: M
authors.lastname: Varra
authors.affiliation: Department of Pharmacy, University of Naples Federico II, via D. Montesano, 49, 80131 Naples, Italy. galeone@unina.it verespos@unina.it.
authors.forename: L
authors.initials: L
authors.lastname: Mayol
authors.affiliation: Department of Pharmacy, University of Naples Federico II, via D. Montesano, 49, 80131 Naples, Italy. galeone@unina.it verespos@unina.it.
authors.forename: V
authors.initials: V
authors.lastname: Esposito
authors.affiliation: Department of Pharmacy, University of Naples Federico II, via D. Montesano, 49, 80131 Naples, Italy. galeone@unina.it verespos@unina.it.
authors.forename: A
authors.initials: A
authors.lastname: Galeone
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001665:Binding Sites; D004591:Electrophoresis, Polyacrylamide Gel; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D013917:Thrombin / Q000737:chemistry*
chemical_list: D052157:Aptamers, Nucleotide; C081676:thrombin aptamer; D013917:Thrombin