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Nucleic Acids Research 2006 34(7):2006-2014; doi:10.1093/nar/gkl144
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Published online 13 April 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Article

NMR solution structures of LNA (locked nucleic acid) modified quadruplexes

Jakob T. Nielsen, Khalil Arar1 and Michael Petersen*

Nucleic Acid Center, Department of Chemistry, University of Southern Denmark Campusvej 55, 5230 Odense M, Denmark 1 Proligo LLC 1 Rue Delaunay, 75011 Paris, France

*To whom correspondence should be addressed. Tel: +45 65 50 25 30; Fax: +45 66 15 87 80; Email: mip{at}chem.sdu.dk

Received January 17, 2006. Revised February 6, 2006. Accepted March 16, 2006.

We have determined the NMR solution structures of the quadruplexes formed by d(TGLGLT) and d(TL4T), where L denotes LNA (locked nucleic acid) modified G-residues. Both structures are tetrameric, parallel and right-handed and the native global fold of the corresponding DNA quadruplex is retained upon introduction of the LNA nucleotides. However, local structural alterations are observed owing to the locked LNA sugars. In particular, a distinct change in the sugar–phosphate backbone is observed at the G2pL3 and L2pL3 base steps and sequence dependent changes in the twist between tetrads are also seen. Both the LNA modified quadruplexes have raised thermostability as compared to the DNA quadruplex. The quadruplex-forming capability of d(TGLGLT) is of particular interest as it expands the design flexibility for stable parallel LNA quadruplexes and shows that LNA nucleotides can be mixed with DNA or other modified nucleic acids. As such, LNA-based quadruplexes can be decorated by a variety of chemical modifications. Such LNA quadruplex scaffolds might find applications in the developing field of nanobiotechnology.


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