title: A new modified thrombin binding aptamer containing a 5'-5' inversion of polarity site.
abstract: The solution structure of a new modified thrombin binding aptamer (TBA) containing a 5'-5' inversion of polarity site, namely d(3'GGT5'-5'TGGTGTGGTTGG3'), is reported. NMR and CD spectroscopy, as well as molecular dynamic and mechanic calculations, have been used to characterize the 3D structure. The modified oligonucleotide is characterized by a chair-like structure consisting of two G-tetrads connected by three edge-wise TT, TGT and TT loops. d(3'GGT5'-5'TGGTGTGGTTGG3') is characterized by an unusual folding, being three strands parallel to each other and only one strand oriented in opposite manner. This led to an anti-anti-anti-syn and syn-syn-syn-anti arrangement of the Gs in the two tetrads. The thermal stability of the modified oligonucleotide is 4 degrees C higher than the corresponding unmodified TBA. d(3'GGT5'-5'TGGTGTGGTTGG3') continues to display an anticoagulant activity, even if decreased with respect to the TBA.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Napoli Federico II, via Cintia, I-80126, Napoli, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Martino
authors.forename: Ada
authors.initials: A
authors.lastname: Virno
authors.forename: Antonio
authors.initials: A
authors.lastname: Randazzo
authors.forename: Antonella
authors.initials: A
authors.lastname: Virgilio
authors.forename: Veronica
authors.initials: V
authors.lastname: Esposito
authors.forename: Concetta
authors.initials: C
authors.lastname: Giancola
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Bucci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirino
authors.forename: Luciano
authors.initials: L
authors.lastname: Mayol
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D052157:Aptamers, Nucleotide; C516250:d(3'-GGT5'-5'TGGTGTGGTTGG3'); C081676:thrombin aptamer; D013917:Thrombin