Journal ArticleDOI
Locked Nucleic Acid (LNA) Recognition of RNA: NMR Solution Structures of LNA:RNA Hybrids
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TLDR
It is suggested that the change in electronic density at the brim of the minor groove, introduced by the LNA modification, is causing an alteration of the pseudorotational profile of the 3'-flanking nucleotide, thus shifting this sugar equilibrium toward N-type conformation.Abstract:
Locked nucleic acids (LNAs) containing one or more 2‘-O,4‘-C-methylene-linked bicyclic ribonucleoside monomers possess a number of the prerequisites of an effective antisense oligonucleotide, e.g. ...read more
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LNAzymes: incorporation of LNA-type monomers into DNAzymes markedly increases RNA cleavage.
Birte Vester,Lars Bo Lundberg,Mads D. Sørensen,B. Ravindra Babu,Stephen Douthwaite,Jesper Wengel +5 more
TL;DR: In comparison with the unmodified DNAzyme, the LNAzymes show significantly improved cleavage of the phosphodiester backbone at the target nucleotide in a small RNA substrate (58n RNA) under single-turnover conditions and show efficient multiple turnover.
Journal ArticleDOI
UNA (unlocked nucleic acid): a flexible RNA mimic that allows engineering of nucleic acid duplex stability.
TL;DR: Synthesis of phosphoramidite UNA building blocks of the nucleobases adenine, cytosine, guanine, and uracil is described herein together with their incorporation into RNA strands.
Journal ArticleDOI
NMR studies of fully modified locked nucleic acid (LNA) hybrids: solution structure of an LNA:RNA hybrid and characterization of an LNA:DNA hybrid.
Katrine E. Nielsen,Jill Rasmussen,Ravindra Kumar,Jesper Wengel,Jens Peter Jacobsen,Michael B. Petersen +5 more
TL;DR: The high-resolution structure reveals that the LNA:RNA hybrid adopts an almost canonical A-type duplex morphology, which shows that fully modified LNA oligomers can hybridize with complementary RNA and form duplexes within the Watson-Crick framework.
Journal ArticleDOI
Improved in situ hybridization efficiency with locked-nucleic-acid-incorporated DNA probes.
TL;DR: The introduction of LNA residues in DNA probes will be a useful approach for effectively enhancing probe hybridization efficiency, and dissociation profiles of the probes revealed that the dissociation temperature was directly related to the number of L NA substitutions and the fluorescence intensity.
Journal ArticleDOI
LNA/DNA chimeric oligomers mimic RNA aptamers targeted to the TAR RNA element of HIV‐1
TL;DR: Evidence is provided that LNA modifications alternated with DNA can generate stable structured RNA mimics for interacting with folded RNA targets and confer good protection towards nuclease digestion.
References
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Journal ArticleDOI
A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP model
TL;DR: In this paper, the authors present an approach to generate electrostatic potential (ESP) derived charges for molecules, which optimally reproduce the intermolecular interaction properties of molecules with a simple two-body additive potential, provided that a suitably accurate level of quantum mechanical calculation is used to derive the ESP around the molecule.
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Antisense oligonucleotides: a new therapeutic principle
Eugen Uhlmann,Anusch Peyman +1 more
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LNA (Locked Nucleic Acids): Synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition
Alexei A. Koshkin,Sanjay K. Singh,Poul Nielsen,Vivek K. Rajwanshi,Ravindra Kumar,Michael Meldgaard,Carl Erik Olsen,Jesper Wengel +7 more
TL;DR: Studies of mis-matched sequences show that LNA obey the Watson-Crick base pairing rules with generally improved selectivities compared to the corresponding unmodified reference strands.
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The ups and downs of nucleic acid duplex stability: Structure-stability studies on chemically-modified DNA:RNA duplexes
TL;DR: From results, structure-activity relationships that correlate hybridization affinity with changes in oligonucleotide structure are determined and C-5-substituted pyrimidines stood out as substantially increasing duplex stability.
Journal ArticleDOI
The Definition of Generalized Helicoidal Parameters and of Axis Curvature for Irregular Nucleic Acids
Richard Lavery,Heinz Sklenar +1 more
TL;DR: An algorithm is presented which solves the problem of obtaining a rigorous helicoidal description of an irregular nucleic acid segment by definition of a function describing simultaneously the curvature of the nucleic acids segment and the corresponding stepwise variation of helicoidal parameters along the segment.