title: NMR studies of fully modified locked nucleic acid (LNA) hybrids: solution structure of an LNA:RNA hybrid and characterization of an LNA:DNA hybrid.
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.
authors.affiliation: Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, 5230 Odense M, Denmark.
authors.forename: Katrine E
authors.initials: KE
authors.lastname: Nielsen
authors.forename: Jill
authors.initials: J
authors.lastname: Rasmussen
authors.forename: Ravindra
authors.initials: R
authors.lastname: Kumar
authors.forename: Jesper
authors.initials: J
authors.lastname: Wengel
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Jacobsen
authors.forename: Michael
authors.initials: M
authors.lastname: Petersen
mesh_terms: D004247:DNA / Q000737:chemistry; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D009692:Nucleic Acid Heteroduplexes; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C477371:locked nucleic acid; D012313:RNA; D004247:DNA