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

We have determined the NMR solution structures of the quadruplexes formed by d(TGLGLT) and d(TL(4)T), 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 up...

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Autores principales: Nielsen, Jakob T., Arar, Khalil, Petersen, Michael
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1435981/
https://www.ncbi.nlm.nih.gov/pubmed/16614450
http://dx.doi.org/10.1093/nar/gkl144
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author Nielsen, Jakob T.
Arar, Khalil
Petersen, Michael
author_facet Nielsen, Jakob T.
Arar, Khalil
Petersen, Michael
author_sort Nielsen, Jakob T.
collection PubMed
description We have determined the NMR solution structures of the quadruplexes formed by d(TGLGLT) and d(TL(4)T), 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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spelling pubmed-14359812006-05-03 NMR solution structures of LNA (locked nucleic acid) modified quadruplexes Nielsen, Jakob T. Arar, Khalil Petersen, Michael Nucleic Acids Res Article We have determined the NMR solution structures of the quadruplexes formed by d(TGLGLT) and d(TL(4)T), 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. Oxford University Press 2006 2006-04-13 /pmc/articles/PMC1435981/ /pubmed/16614450 http://dx.doi.org/10.1093/nar/gkl144 Text en © The Author 2006. Published by Oxford University Press. All rights reserved
spellingShingle Article
Nielsen, Jakob T.
Arar, Khalil
Petersen, Michael
NMR solution structures of LNA (locked nucleic acid) modified quadruplexes
title NMR solution structures of LNA (locked nucleic acid) modified quadruplexes
title_full NMR solution structures of LNA (locked nucleic acid) modified quadruplexes
title_fullStr NMR solution structures of LNA (locked nucleic acid) modified quadruplexes
title_full_unstemmed NMR solution structures of LNA (locked nucleic acid) modified quadruplexes
title_short NMR solution structures of LNA (locked nucleic acid) modified quadruplexes
title_sort nmr solution structures of lna (locked nucleic acid) modified quadruplexes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1435981/
https://www.ncbi.nlm.nih.gov/pubmed/16614450
http://dx.doi.org/10.1093/nar/gkl144
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