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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Dissertation
Vergleichende Analyse der anti-Bcl-2 Antisense-Oligonukleotide SPC2996 und Oblimersen in präklinischen Modellen der chronischen lymphatischen Leukämie
TL;DR: Oblimersen et al. as discussed by the authors investigated the anti-Bcl-2 Antisense Oligonukleotide (AODN) in vitro and in vivo, i.e., the AODN was used to regulate the Zielstruktur of CLL-Zellen.
Journal ArticleDOI
Influence of Sugar Modifications on the Nucleoside Conformation and Oligonucleotide Stability: A Critical Review
TL;DR: This review systematically categorise various ribofuranose sugar modifications employed in DNAs and RNAs so far and discusses different stereoelectronic effects imparted by different substituents on the sugar ring and how these effects control sugar puckering.
Journal ArticleDOI
How RNase HI (Escherichia coli) promoted site-selective hydrolysis works on RNA in duplex with carba-LNA and LNA substituted antisense strands in an antisense strategy context?
TL;DR: The enhancement of the total rate of cleavage of the complementary mRNA strand by up to 25%, presented in this work, provides opportunities to engineer a single modification site in appropriately substituted AONs to design an effective antisense strategy based on the nucleolytic stability of the AON strand versus RNase H capability to cleave the complementary RNA strand.
Journal ArticleDOI
Convertible and Constrained Nucleotides: The 2'-Deoxyribose 5'-C-Functionalization Approach, a French Touch.
TL;DR: In this article, the 5'-C position of the nucleoside sugar was modified to allow the introduction of an additional chemical handle at any position on the nucleotide chain without disturbing the Watson-Crick base-pairing.
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.