α-LNA (Locked Nucleic Acid withα-D-Configuration): Synthesis and Selective Parallel Recognition of RNA

Nielsen, Poul; Christensen, Nanna K.; Dalskov, Jakob K.

doi:10.1002/1521-3765(20020201)8:3<712::aid-chem712>3.0.co;2-0

Cited by 24 publications

(19 citation statements)

References 59 publications

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“…Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. [6,7] The former was DMT-protected and converted by standard steps into two different phosphoramidites of either the thymine or the N-4benzoyl-5-methylcytosine a-LNA monomers. [4,5] However, these have been restricted towards S-type conformations [4,5] which are also the conformations preferred by a-DNA.…”

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confidence: 99%

“…Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions a-DNA that contains bicyclic a-configured nucleosides have been introduced. [7] These as well as the two corresponding a-DNA phosphoramidites were used as building blocks for oligonucleotide sequences (Table 1). Subsequently, a-LNA is the first a-DNA analogue to be restricted in an N-type conformation due to the locked bicyclic carbohydrate skeleton.…”

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confidence: 99%

“…[4,5] However, these have been restricted towards S-type conformations [4,5] which are also the conformations preferred by a-DNA. [7] In a-DNA=a-LNA mixmers, the exchange of one or six a-DNA monomers with a-LNA monomers results in strongly decreased affinity against both DNA and RNA when compared to the unmodified a-DNA sequence. [6,7] The successful synthesis of the a-LNA thymine monomer was accomplished from diacetone-a-D-allose through standard steps ending with a Vorbrü ggen nucleobase coupling reaction, a ring-closing reaction and, subsequently, separation of the aand (b-) LNA monomers.…”

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confidence: 99%

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α-LNA (α-D-Configured Locked Nucleic Acid)

Christensen

Petersen

Vester

et al. 2003

Nucleosides, Nucleotides and Nucleic Acids

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α-LNA (α-D-Configured Locked Nucleic Acid)

Christensen

Petersen

Vester

et al. 2003

Nucleosides, Nucleotides and Nucleic Acids

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“…Structural studies have revealed that, whereas LNA in structural terms is a true RNA-mimic, a-L-LNA can be considered as a DNA-mimic due to the B-type mimicking properties of a-L-LNA sequences [67]. The strong affinity for complementary RNA found for a-D-LNA forming a parallel duplex was more expected, although a structure which is seemingly different from other parallel duplexes has been indicated [68]. As a consequence of a-L-LNA being a DNA-mimic, b-L-LNA was investigated as an a-DNA mimic, and indeed, stable parallel duplexes with both complementary RNA and DNA were demonstrated in a mirror-image study [69].…”

Section: Analogues Of Lna and Their Structural Impactmentioning

confidence: 99%

Locked Nucleic Acids: Properties, Applications, and Perspectives

Nielsen

Wengel

2008

Modified Nucleosides

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A decade has passed since the introduction of locked nucleic acid (LNA) [1][2][3]. This chapter provides a review and a current status on the features and applications of LNA. Attention is focused on the structural chemistry of LNA and on its applications for therapeutics and probes. With regards to the latter point, the chapter is based on former comprehensive reviews on LNA applications [4][5][6] and, for that reason, is focused on results reported subsequently, with no intention of being comprehensive.The field of nucleic acid chemistry has evolved considerably during the past few decades, leading from synthetic developments via molecular recognition into nucleic acid-based therapeutics, powerful diagnostic probes, and modern nanobiotechnology. From the structural perspective, the central issue has been the thorough understanding of the basis for molecular recognition and the selective formation of nucleic acid complexes, initially the classic Watson-Crick-type double helix. The central creative challenge for synthetic chemists has been to design simple chemical perturbations of the natural duplex in order to increase our knowledge within nucleic acid chemical biology, and to bring this knowledge into applied nucleic acids research [7-9].The major motivation behind the design of nucleic acid analogues has, over the past two decades, been the antisense strategy aimed at the silencing of genes by strong binding towards mRNA, with or without associated RNA-cleavage. Two central problems have motivated the chemical effort: (1) the physiological instability of natural oligonucleotides; and (2) the relatively moderate affinity of short natural oligonucleotides for their RNA-targets [10,11]. If a solution to these problems -as well as to the delicate question of cellular delivery -can be found, then oligonucleotides will present unlimited therapeutic perspectives. Among the more than 1000 chemical analogues tested for these properties, a large part seems to induce a high degree of resistance towards nucleolytic degradation, although this is dependent on the sequence composition, the number and positioning of the chemical modifications within the sequence, and on the degree of perturbation compared to the natural chemical structure. On the other hand, significantly increasing the RNA-affinity of an Modified Nucleosides: in Biochemistry, Biotechnology and Medicine. Edited by Piet Herdewijn

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“…(4)). Fully modified -D-LNA sequences of either oligothymine or mixed oligopyrimidines, displayed unprecedented recognition of parallel complementary RNA sequences whereas the complementary DNA sequences were not recognized [33,34]. Chimeric -D-LNA/ -DNA sequences showed low affinity for RNA.…”

Section: Enantio-dna and Other Stereoisomers Of Dna/rnamentioning

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Structure-Editing of Nucleic Acids for Selective Targeting of RNA

Kumar¹,

Ganesh

2007

CTMC

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The synthesis of backbone-modified nucleic acids has been an area of very intense research over the last two decades. The main reason for this research activity is the instability of nucleic acid based drugs in the intracellular conditions. Changes in the sugar-phosphate backbone invariably bring about the changes in the complementation properties of the nucleic acids. The naturally occurring deoxyribose- (DNA) and ribose (RNA) sugar-phosphate backbones are endowed with considerable differences in their binding affinities towards themselves. This occurs because of the different sugar conformations prevalent in DNA and RNA and the subtle structural changes accruing from these in hydrogen bonding, base-stacking interactions and hydration of major/minor grooves. The six-atom phosphodiester linkages and pentose-sugars give immense opportunities for chemical modifications that lead to several backbone-modified nucleic acid structures. This article is focused on such modifications that impart RNA-selective binding properties to the modified nucleic acid mimics and the rationale behind the said selectivity. It is found that the six-atom sugar-phosphate backbone could be replaced by either one-atom extended or one-atom edited repeating units, leading to the folded or extended geometries to maintain the internucleoside distance-complementarity. Other important contributions come from electronegativity of the substituent groups, hydration in the major/minor groove, base stacking etc.

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α-LNA (Locked Nucleic Acid withα-D-Configuration): Synthesis and Selective Parallel Recognition of RNA

Cited by 24 publications

References 59 publications

α-LNA (α-D-Configured Locked Nucleic Acid)

α-LNA (α-D-Configured Locked Nucleic Acid)

Locked Nucleic Acids: Properties, Applications, and Perspectives

Structure-Editing of Nucleic Acids for Selective Targeting of RNA

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