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Published online 4 June 2004

Nucleic Acids Research, 2004, Vol. 32, No. 10 3083-3092
© 2004 Oxford University Press

NMR solution structure of a parallel LNA quadruplex

Antonio Randazzo, Veronica Esposito, Oliver Ohlenschläger1, Ramadurai Ramachandran1 and Luciano Mayol*

Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli ‘Federico II’, via D. Montesano 49, I-80131 Napoli, Italy and 1 Institut für Molekulare Biotechnologie, Abt. Molekulare Biophysik/NMR-Spektroskopie, Beutenbergstr. 11, D-07745 Jena, Germany

*To whom correspondence should be addressed. Tel: +39 081 678508; Fax: +39 081 678552; Email: mayoll{at}unina.it

Received January 28, 2004; Revised and Accepted May 11, 2004

The solution structure of a locked nucleic acid (LNA) quadruplex, formed by the oligomer d(TGGGT), containing only conformationally restricted LNA residues is reported. NMR and CD spectroscopy, as well as molecular dynamics and mechanic calculations, has been used to characterize the complex. The molecule adopts a parallel stranded conformation with a 4-fold rotational symmetry, showing a right-handed helicity and the guanine residues in an almost planar conformation with three well-defined G-tetrads. The thermal stability of Q-LNA has been found to be comparable with that of [r(UGGGU)]4, while a Tm increment of 20°C with respect to the corresponding DNA quadruplex structure [d(TGGGT)]4 has been observed. The structural features of the LNA quadruplex reported here may open new perspectives for the biological application of LNAs as novel versatile tools to design aptamer or catalyst oligonucleotides.


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