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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Chemically modified oligonucleotides with efficient RNase H response.
Birte Vester,Anne Marie Boel,Sune Lobedanz,B. Ravindra Babu,Michael Raunkjær,Dorthe Lindegaard,Raunak,Patrick J. Hrdlicka,Torben Højland,Pawan K. Sharma,Pawan K. Sharma,Surender Kumar,Poul Nielsen,Jesper Wengel +13 more
TL;DR: Ten different chemically modified nucleosides were incorporated into short DNA strands (chimeric oligonucleotides ON3-ON12 and ON15-ON24) and then tested for their capacity to mediate RNAse H cleavage of the complementary RNA strand and there seems to be no correlation between the thermal stability between the duplexes and RNase H cleaving.
Journal ArticleDOI
Biophysical studies of DNA modified with conformationally constrained nucleotides: comparison of 2′-exo (north) and 3′-exo (south) ‘locked’ templates
TL;DR: The data suggest that although DNA can tolerate modifications with RNA-like (North) nucleotides, a more complicated spectrum of changes emerges with modifications restricted to South (DNA-like) puckers.
Journal ArticleDOI
Effect of locked nucleic acid modifications on the thermal stability of noncanonical DNA structure.
Jhimli Bhattacharyya,Souvik Maiti,Sanjukta Muhuri,Shu-ichi Nakano,Daisuke Miyoshi,Naoki Sugimoto +5 more
TL;DR: Quantitative parameters demonstrated that LNA modification specifically stabilized the noncanonical parallel duplex, and can be useful in the rational design of functional molecules such as more effective antisense and antigene strands, more sensitive strands for detection of target DNA and RNA strands, and molecular switches responding to solution pH.
Journal ArticleDOI
NMR and UV studies of 3'-S-phosphorothiolate modified DNA in a DNA : RNA hybrid dodecamer duplex; implications for antisense drug design.
Andrew P. G. Beevers,Kevin J. Fettes,Ghalia Sabbagh,Fatima K. Murad,John R. P. Arnold,Richard Cosstick,Julie Fisher +6 more
TL;DR: High-resolution NMR spectroscopy has been used to establish the conformational consequences of the introduction of a single 3[prime or minute]-S-phosphorothiolate link in the DNA strand of a DNA : RNA hybrid, indicative of an additive effect of the modification with thermodynamic benefit being derived from alternate spacing of two modified linkers.
Journal ArticleDOI
An α-d-Configured Bicyclic Nucleoside Restricted in an E-type Conformation: Synthesis and Parallel RNA Recognition
TL;DR: The present bicyclic analogue represents the first conformationally restricted alpha- DNA-analogue to improve nucleic acid recognition in mixmers with alpha-DNA monomers.
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.