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
Citations
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MicroRNA detection by northern blotting using locked nucleic acid probes
TL;DR: An improved protocol for miRNA northern blot analysis is described, which includes RNA extraction, polyacrylamide gel electrophoresis and northern blotting, and the hybridization and detection of locked nucleic acid (LNA)-modified oligonucleotide probes.
Journal ArticleDOI
Inhibition of microRNA function by antimiR oligonucleotides
TL;DR: This review focuses on the use of antisense oligonucleotides (antimiRs) in miRNA inhibition for loss-of-function studies and summarizes recent progress in antimiR mediated pharmacological inhibition of disease-associated miRNAs, which shows great promise in the development of novel miRNA-based therapeutics.
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Chemical modification and design of anti-miRNA oligonucleotides
Kim A. Lennox,Mark A. Behlke +1 more
TL;DR: Antisense techniques that employ synthetic oligonucleotides have been used to study miRNA function and some of these compounds may have potential as novel drug candidates to intervene in diseases where miRNAs contribute to the underlying pathophysiology.
Journal ArticleDOI
Design of LNA probes that improve mismatch discrimination
TL;DR: Forescence experiments using 2-aminopurine suggest that LNA modifications enhance base stacking of perfectly matched base pairs and decrease stabilizing stacking interactions of mismatched base pairs, and new guidelines are suggested for design of LNA probes, which significantly improve mismatch discrimination in comparison with unmodified DNA probes.
Journal ArticleDOI
Perspectives on Chemistry and Therapeutic Applications of Locked Nucleic Acid (LNA)
TL;DR: LNA as a Tool: Implications 4684 3.1.3.2 LNA in Diagnostics 4689 3.2.4.
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.