NMR Studies of Fully Modified Locked Nucleic Acid (LNA) Hybrids: Solution Structure of an LNA:RNA Hybrid and Characterization of an LNA:DNA Hybrid
- 1 May 2004
- journal article
- research article
- Published by American Chemical Society (ACS) in Bioconjugate Chemistry
- Vol. 15 (3), 449-457
- https://doi.org/10.1021/bc034145h
Abstract
LNA is a bicyclic nucleic acid analogue that contains one or more 2‘-O,4‘-C methylene linkage(s), which effectively locks the furanose ring in a C3‘-endo conformation. We report here the NMR solution structure of a nonamer LNA:RNA hybrid and a structural characterization of a nonamer LNA:DNA hybrid, where the LNA strands are composed entirely of LNA nucleotides. This is the first structural characterization of fully modified LNA oligonucleotides. The high-resolution structure reveals that the LNA:RNA hybrid adopts an almost canonical A-type duplex morphology. The helix axis is almost straight and the duplex geometry is regular. This shows that fully modified LNA oligomers can hybridize with complementary RNA and form duplexes within the Watson−Crick framework. The LNA:DNA hybrid structurally resembles an RNA:DNA hybrid as shown by determination of deoxyribose sugar puckers and analysis of NOESY NMR spectra.Keywords
This publication has 22 references indexed in Scilit:
- LNA: a versatile tool for therapeutics and genomicsTrends in Biotechnology, 2003
- LNAzymes: Incorporation of LNA-Type Monomers into DNAzymes Markedly Increases RNA CleavageJournal of the American Chemical Society, 2002
- α-l-ribo-Configured Locked Nucleic Acid (α-L-LNA): Synthesis and PropertiesJournal of the American Chemical Society, 2002
- Synthesis of Abasic Locked Nucleic Acid and Twoseco-LNA Derivatives and Evaluation of Their Hybridization Properties Compared with Their More Flexible DNA CounterpartsThe Journal of Organic Chemistry, 2000
- Ab Initio Quantum Mechanical Study of the Structures and Energies for the Pseudorotation of 5‘-Dehydroxy Analogues of 2‘-Deoxyribose and Ribose SugarsJournal of the American Chemical Society, 1999
- LNA (Locked Nucleic Acid): An RNA Mimic Forming Exceedingly Stable LNA:LNA DuplexesJournal of the American Chemical Society, 1998
- Solution structure sf r(gaggacug):d(CAGTCCTC) hybrid: implications for the initiation of HIV-1(+)-strand synthesisJournal of Molecular Biology, 1997
- Structure of a DNA : RNA Hybrid DuplexJournal of Molecular Biology, 1993
- A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP modelThe Journal of Physical Chemistry, 1993
- Sequential resonance assignments in DNA proton NMR spectra by two-dimensional NOE spectroscopyJournal of the American Chemical Society, 1983