A new modified thrombin binding aptamer containing a 5'?5' inversion of polarity site - Aptamers

A new modified thrombin binding aptamer containing a 5'?5' inversion of polarity site
December 1, 2006
Luigi Martino, Ada Virno1, Antonio Randazzo1, Antonella Virgilio1, Veronica Esposito1, Concetta Giancola, Mariarosaria Bucci2, Giuseppe Cirino2 and Luciano Mayol1,*
Dipartimento di Chimica, Universit? degli Studi di Napoli ?Federico II? via Cintia, I-80126, Napoli, Italy 1 Dipartimento di Chimica delle Sostanze Naturali, Universit? degli Studi di Napoli ?Federico II? via D. Montesano 49, I-80131 Napoli, Italy 2 Dipartimento di Farmacologia Sperimentale, Universit? degli Studi di Napoli ?Federico II? via D. Montesano 49, I-80131 Napoli, Italy
Nucleic Acids Research
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?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.
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