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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Locked nucleic acids: a family of high affinity nucleic acid probes
TL;DR: The structure and synthesis of LNA (locked nucleic acid) is presented and the improved synthesis of the thymine LNA monomer is shown.
Journal ArticleDOI
The development and improvement of ribonucleic acid therapy strategies.
Yuxi Zhao,Rui Shu,Jiang Liu +2 more
TL;DR: A review of RNA therapeutic drugs and their internal connections is presented in this article, where various chemical modifications and delivery systems used to improve the performance of these drugs and overcome their limitations are discussed.
Journal ArticleDOI
Investigation of catalysis by bacterial RNase P via LNA and other modifications at the scissile phosphodiester
TL;DR: The strong catalytic defect for LNA and 2′-OCH3 supports a model where the extra methylene (LNA) or methyl group causes a steric interference with a nearby bound catalytic Mg2+ during its recoordination on the way to the transition state for cleavage.
Journal ArticleDOI
Targeting MicroRNAs Involved in the BDNF Signaling Impairment in Neurodegenerative Diseases.
TL;DR: The specific molecular mechanisms by which several miRNAs negatively modulate the expressions of BDNF are summarized, the potential clinical difficulties that can be faced during the development of anti-miRNA-based therapeutics are addressed and strategies to overcome these challenges are proposed.
Journal ArticleDOI
Enhanced recognition of non-complementary hybridization by single-LNA-modified oligonucleotide probes
TL;DR: It was observed that LNA modification indeed improves the discrimination capability of oligonucleotides by increasing the melting temperature differences between the complementary duplexes and hybrids containing mismatches.
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
Journal ArticleDOI
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.