NMR solution structures of LNA (locked nucleic acid) modified quadruplexes
Open Access
- 13 April 2006
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 34 (7), 2006-2014
- https://doi.org/10.1093/nar/gkl144
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.Keywords
This publication has 38 references indexed in Scilit:
- The effect of chemical modifications on the thermal stability of different G-quadruplex-forming oligonucleotidesNucleic Acids Research, 2005
- Biophysical properties of quadruple helices of modified human telomeric DNAPeptide Science, 2004
- NMR Studies of Fully Modified Locked Nucleic Acid (LNA) Hybrids: Solution Structure of an LNA:RNA Hybrid and Characterization of an LNA:DNA HybridBioconjugate Chemistry, 2004
- Nucleic acid nanotechnology—towards Ångström-scale engineeringOrganic & Biomolecular Chemistry, 2003
- Telomere Inhibition and Telomere Disruption as Processes for Drug TargetingAnnual Review of Pharmacology and Toxicology, 2003
- LNA: a versatile tool for therapeutics and genomicsTrends in Biotechnology, 2003
- Protein NMR Structure Determination with Automated NOE Assignment Using the New Software CANDID and the Torsion Angle Dynamics Algorithm DYANAJournal of Molecular Biology, 2002
- Life at the End of the Chromosome: Telomeres and TelomeraseAngewandte Chemie, 2000
- Biologically active oligodeoxyribonucleotides. Part 11: The least phosphate-modification of quadruplex-forming hexadeoxyribonucleotide TGGGAG, bearing 3′- and 5′-end-modification, with anti-HIV-1 activityBioorganic & Medicinal Chemistry, 1998
- Sequence-specific Binding Protein of Single-stranded and Unimolecular Quadruplex Telomeric DNA from Rat HepatocytesOnline Journal of Public Health Informatics, 1997