Structures, Dynamics, and Stabilities of Fully Modified Locked Nucleic Acid (β-d-LNA and α-l-LNA) Duplexes in Comparison to Pure DNA and RNA Duplexes

2013 ◽  
Vol 117 (18) ◽  
pp. 5556-5564 ◽  
Author(s):  
Gorle Suresh ◽  
U. Deva Priyakumar
Keyword(s):  
Nucleic Acid ◽  
Locked Nucleic Acid ◽  
Dna And Rna ◽  
Rna Duplexes

scholarly journals Oligonucleotide-based systems: DNA, microRNAs, DNA/RNA aptamers

2016 ◽  
Vol 60 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Pawan Jolly ◽  
Pedro Estrela ◽  
Michael Ladomery
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Rna Aptamers ◽  
Locked Nucleic Acid ◽  
Synthetic Analogue ◽  
Dna And Rna ◽  
Naturally Occurring ◽  
Wide Range ◽  
Synthetic Oligonucleotides ◽  
Shed Light

There are an increasing number of applications that have been developed for oligonucleotide-based biosensing systems in genetics and biomedicine. Oligonucleotide-based biosensors are those where the probe to capture the analyte is a strand of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or a synthetic analogue of naturally occurring nucleic acids. This review will shed light on various types of nucleic acids such as DNA and RNA (particularly microRNAs), their role and their application in biosensing. It will also cover DNA/RNA aptamers, which can be used as bioreceptors for a wide range of targets such as proteins, small molecules, bacteria and even cells. It will also highlight how the invention of synthetic oligonucleotides such as peptide nucleic acid (PNA) or locked nucleic acid (LNA) has pushed the limits of molecular biology and biosensor development to new perspectives. These technologies are very promising albeit still in need of development in order to bridge the gap between the laboratory-based status and the reality of biomedical applications.

The effect of LNA nucleobases as enhancers for the binding of amiloride to an abasic site in DNA/DNA and DNA/RNA duplexes

2014 ◽  
Vol 12 (37) ◽  
pp. 7250-7256 ◽  
Author(s):  
Yusuke Sato ◽  
Tetsushi Sato ◽  
Takaya Sato ◽  
Seiichi Nishizawa ◽  
Norio Teramae
Keyword(s):  
Nucleic Acid ◽  
Locked Nucleic Acid ◽  
Dna Duplexes ◽  
Abasic Site ◽  
Rna Duplexes

We report on a significant effect of locked nucleic acid (LNA) nucleobases on the binding of amiloride for abasic site (AP)-containing DNA duplexes.

Thermodynamics of nucleic acids and their interactions with ligands

2000 ◽  
Vol 33 (3) ◽  
pp. 255-306 ◽  
Author(s):  
Andrew N. Lane ◽  
Terence C. Jenkins
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Large Scale ◽  
Wide Spectrum ◽  
Model Systems ◽  
Linear Polymers ◽  
Dna And Rna ◽  
Rna Duplexes ◽  
Scale Properties ◽  
Folded Structures

1. Introduction 2551.1 General thermodynamics 2562. Nucleic acid thermodynamics 2602.1 DNA duplexes 2612.2 RNA duplexes 2632.3 Hybrid DNA–RNA duplexes 2642.4 Hydration 2672.5 Conformational flexibility 2692.6 Thermodynamics 2723. Nucleic acid–ligand interactions 2773.1 Minor groove binders 2783.2 DNA intercalators 2843.3 Triple-helical systems 2883.3.1 Structures 2883.3.2 Hydration 2913.3.3 Thermodynamics 2914. Conclusions 2955. Acknowledgements 2986. References 298In recent years the availability of large quantities of pure synthetic DNA and RNA has revolutionised the study of nucleic acids, such that it is now possible to study their conformations, dynamics and large-scale properties, and their interactions with small ligands, proteins and other nucleic acids in unprecedented detail. This has led to the (re)discovery of higher order structures such as triple helices and quartets, and also the catalytic activity of RNA contingent on three-dimensional folding, and the extraordinary specificity possible with DNA and RNA aptamers.Nucleic acids are quite different from proteins, even though they are both linear polymers formed from a small number of monomeric units. The major difference reflects the nature of the linkage between the monomers. The 5′–3′ phosphodiester linkage in nucleic acids carries a permanent negative charge, and affords a relatively large number of degrees of freedom, whereas the essentially rigid planar peptide linkage in proteins is neutral and provides only two degrees of torsional freedom per backbone residue. These two properties conspire to make nucleic acids relatively flexible and less likely to form extensive folded structures. Even when true 3D folded structures are formed from nucleic acids, the topology remains simple, with the anionic phosphates forming the surface of the molecule. Nevertheless, nucleic acids do occur in a variety of structures that includes single strands and high-order duplex, triplex or tetraplex (‘quadruplex’) forms. The principles of biological recognition and the related problem of understanding the forces that stabilise such folded structures are in some respects more straightforward than for proteins, making them attractive model systems for understanding general biophysical problems. This view is aided by the relatively facile chemical synthesis of pure nucleic acids of any desired size and defined sequence, and the ease of incorporation of a wide spectrum of chemically modified bases, sugars and backbone linkers. Such modifications are considerably more difficult to achieve with oligopeptides or proteins.

Thermodynamic and Kinetic Characterization of Duplex Formation between 2′-O, 4′-C-Methylene-modified Oligoribonucleotides, DNA and RNA

2007 ◽  
Vol 27 (6) ◽  
pp. 327-333 ◽  
Author(s):  
Ulla Christensen
Keyword(s):  
Nucleic Acid ◽  
Full Length ◽  
Locked Nucleic Acid ◽  
Complementary Dna ◽  
High Affinity ◽  
Thermodynamics And Kinetics ◽  
Dna And Rna ◽  
Reaction Thermodynamics ◽  
Duplex Formation

2′-O,4′-C-methylene-linked ribonucleotide derivatives, named LNA (locked nucleic acid) and BNA (bridged nucleic acid) are nucleic acid analogoues that have shown high-affinity recognition of DNA and RNA, and the employment of LNA oligomers for antisense activity, gene regulation and nucleic acid diagnostics seems promising. Here we show kinetic and thermodynamic results on the interaction of a series of 10 bases long LNA–DNA mixmers, gabmers as well as full length LNA's with the complementary DNA, RNA and LNA oligonucleotides in the presence and absence of 10 mM Mg2+- ions. Our results show no significant differences in the reaction thermodynamics and kinetics between the LNA species, only a tendency to stronger duplex formation with the gabmer and mixmer. Introduction of a few LNA's thus may be a better strategy, than using full length LNA's to obtain an oligonucleotide that markedly increases the strength of duplexes formed with the complementary DNA and RNA.

scholarly journals Symmetry in Nucleic-Acid Double Helices

Symmetry ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 737
Author(s):  
Udo Heinemann ◽  
Yvette Roske
Keyword(s):  
Nucleic Acid ◽  
Base Pair ◽  
Rna Structure ◽  
Test Tube ◽  
Base Pairs ◽  
Dna And Rna ◽  
Left Handed ◽  
Double Helices ◽  
Rna Duplexes ◽  
The Right

In nature and in the test tube, nucleic acids occur in many different forms. Apart from single-stranded, coiled molecules, DNA and RNA prefer to form helical arrangements, in which the bases are stacked to shield their hydrophobic surfaces and expose their polar edges. Focusing on double helices, we describe the crucial role played by symmetry in shaping DNA and RNA structure. The base pairs in nucleic-acid double helices display rotational pseudo-symmetry. In the Watson–Crick base pairs found in naturally occurring DNA and RNA duplexes, the symmetry axis lies in the base-pair plane, giving rise to two different helical grooves. In contrast, anti-Watson–Crick base pairs have a dyad axis perpendicular to the base-pair plane and identical grooves. In combination with the base-pair symmetry, the syn/anti conformation of paired nucleotides determines the parallel or antiparallel strand orientation of double helices. DNA and RNA duplexes in nature are exclusively antiparallel. Watson–Crick base-paired DNA or RNA helices display either right-handed or left-handed helical (pseudo-) symmetry. Genomic DNA is usually in the right-handed B-form, and RNA double helices adopt the right-handed A-conformation. Finally, there is a higher level of helical symmetry in superhelical DNA in which B-form double strands are intertwined in a right- or left-handed sense.

Stopped-flow kinetics of locked nucleic acid (LNA)–oligonucleotide duplex formation: studies of LNA–DNA and DNA–DNA interactions

2001 ◽  
Vol 354 (3) ◽  
pp. 481-484 ◽  
Author(s):  
Ulla CHRISTENSEN ◽  
Nana JACOBSEN ◽  
Vivek K. RAJWANSHI ◽  
Jesper WENGEL ◽  
Troels KOCH
Keyword(s):  
Nucleic Acid ◽  
Dissociation Constants ◽  
Locked Nucleic Acid ◽  
Stopped Flow ◽  
Complementary Dna ◽  
Conformationally Restricted ◽  
Dna And Rna ◽  
Melting Curves ◽  
Oligonucleotide Duplex ◽  
Duplex Formation

The locked nucleic acid (LNA) monomer is a conformationally restricted nucleotide analogue with an extra 2′-O,4′-C-methylene bridge added to the ribose ring. Oligonucleotides that contain LNA monomers have shown greatly enhanced thermal stability when hybridized to complementary DNA and RNA and are considered most promising candidates for efficient recognition of a given mixed sequence in a nucleic acid duplex and as an antisense molecule. Here the kinetics and thermodynamics of a series of oligonucleotide duplex formations of DNA–DNA and DNA–LNA octamers were studied using stopped-flow absorption measurements at 25°C and melting curves. The reactions of the DNA octamer 5′-CAGGAGCA-3′ with its complementary DNA octamer 5′-TGCTCCTG-3′, and with the LNA octamers 5′-TLGCTCCTG-3′ (LNA-1), 5′-TLGCTLCCTG-3′ (LNA-2) and 5′-TLGCTLCCTLG-3′(LNA-3), containing respectively one, two or three thymidine 2′-O,4′-C-methylene-(D-ribofuranosyl) nucleotide monomers, designated TL, were studied. In all cases were seen fast second-order association reactions with kobs = 2×107M-1˙s-1. At 25°C the dissociation constants of the duplexes obtained from melting curves were: DNA–DNA, 10nM; DNA–LNA-1, 20nM; DNA–LNA-2, 2nM; and DNA–LNA-3, 0.3nM; thus the greatly enhanced duplex stability induced by LNA is confirmed. Since the association rates were all equal this increase in stability is due to slower rates of dissociation of the complexes.

High-resolution nucleic acid sequence mapping via in situ hybridization at the Electron Microscope level

1995 ◽  
Vol 53 ◽  
pp. 752-753
Author(s):  
B.A. Hamkalo ◽  
S. Narayanswami ◽  
A.P. Kausch
Keyword(s):  
Nucleic Acid ◽  
Interphase Nucleus ◽  
Genome Mapping ◽  
Precise Location ◽  
Electron Microscope Level ◽  
Rna Sequences ◽  
Fundamental Interest ◽  
Whole Cells ◽  
Dna And Rna

The availability of nonradioactive methods to label nucleic acids an the resultant rapid and greater sensitivity of detection has catapulted the technique of in situ hybridization to become the method of choice to locate of specific DNA and RNA sequences on chromosomes and in whole cells in cytological preparations in many areas of biology. It is being applied to problems of fundamental interest to basic cell and molecular biologists such as the organization of the interphase nucleus in the context of putative functional domains; it is making major contributions to genome mapping efforts; and it is being applied to the analysis of clinical specimens. Although fluorescence detection of nucleic acid hybrids is routinely used, certain questions require greater resolution. For example, very closely linked sequences may not be separable using fluorescence; the precise location of sequences with respect to chromosome structures may be below the resolution of light microscopy(LM); and the relative positions of sequences on very small chromosomes may not be feasible.

scholarly journals Sulfur Modification in Natural RNA and Therapeutic Oligonucleotides

2021 ◽  
Author(s):  
Ya Ying Zheng ◽  
Ying Wu ◽  
Thomas Begley ◽  
Jia Sheng
Keyword(s):  
Nucleic Acid ◽  
Dna And Rna ◽  
Sulfur Modification ◽  
Oxygen Atoms

Sulfur modifications have been discovered on both DNA and RNA. Sulfur substitution of oxygen atoms at nucleobase or backbone locations in the nucleic acid framework led to a wide variety...

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