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

Abstract:

: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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Nielsen JT,Arar K,Petersen M

doi

10.1093/nar/gkl144

subject

Has Abstract

pub_date

2006-04-13 00:00:00

pages

2006-14

issue

7

eissn

0305-1048

issn

1362-4962

pii

34/7/2006

journal_volume

34

pub_type

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