LNA (LOCKED NUCLEIC ACID) AND THE DIASTEREOISOMERIC Α-L-Lna: CONFORMATIONAL TUNING AND HIGH-AFFINITY RECOGNITION OF DNA/RNA TARGETS

Wengel, Jesper; Petersen, Michael; Nielsen, Kathrine E.; Jensen, Gitte A.; Håkansson, Anders E.; Kumar, Ravindra; Sørensen, Mads D.; Rajwanshi, Vivek K.; Bryld, Torsten; Jacobsen, Jens Peter

doi:10.1081/ncn-100002312

Cited by 61 publications

(49 citation statements)

References 16 publications

(9 reference statements)

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“…The exchange of three thymidine monomers by three thymine LNA monomers (cf., entry 2, oxy-LNA/DNA chimera) induced substantially increased thermal affinities towards both complementary DNA and RNA [8,9]. Even higher Tm values were obtained for the corresponding oxy-LNA/RNA chimera [25] (cf., entry 3), the fully modified LNA [8] (cf., entry 4) and an LNA/2' -O-methyl-RNA chimera (cf., entry 5) [26].…”

Section: Hybridization Characteristics Of Lna Oligonucleotidesmentioning

confidence: 98%

“…One LNA diastereoisomer, namely a-L-LNA, has been studied intensively and has shown very efficient recognition of complementary strands, in particular complementary RNA [19,22,23,26,28,29]. Accordingly, incorporation of three 2'-O,4'-C-methyleneot-L-ribofuranosyl thymine ot-L-LNA monomers into either a DNA strand [28] (cf., entry 9, ot-L-LNA/DNA chimera) or a 2'-OMe-RNA strand [26] (cf., entry 10, ot-L-LNA/2'-OMe-RNA chimera) lead to significantly increased Tm values.…”

Section: Hybridization Characteristics Of Lna Oligonucleotidesmentioning

confidence: 99%

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Chemistry of locked nucleic acids (LNA): Design, synthesis, and bio-physical properties

Wengel

Petersen

Frieden³

et al. 2003

Lett Pept Sci

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SummaryPreparation of LNA nucleosides requires a number of synthetic steps but very efficient procedures have been developed, as have protocols for synthesis of LNA oligonucleotides on automated DNA synthesizers. In all cases, LNA oligonucleotides have exhibited good aqueous solubility as would be expected from their close structural resemblance to the natural nucleic acids. The universality of LNA mediated high-affinity and specific hybridization has been demonstrated extensively with a large number of duplex forming LNA-oligonucleotides. Most importantly, most of the members of the LNA molecular family have been shown to exert their substantial affinity increase (i) in combination with standard DNA, RNA and contemporary analogues and (ii) whether inserted as single nucleosides in an oligonucleotide or as blocks of contiguous nucleotides, an important point. The works on TFO's is expanding the usefulness of LNA to double strand recognition and it has been demonstrated that LNA it is a promising structure for further base modifications in the pursuit of global sequence specific recognition of DNA.

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Section: Hybridization Characteristics Of Lna Oligonucleotidesmentioning

confidence: 98%

Section: Hybridization Characteristics Of Lna Oligonucleotidesmentioning

confidence: 99%

Chemistry of locked nucleic acids (LNA): Design, synthesis, and bio-physical properties

Wengel

Petersen

Frieden³

et al. 2003

Lett Pept Sci

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“…Recent years, many studies confirm LNAs take advantages of low toxicity [18], enhanced triplex formation [19 -21], nuclease resistance [15,22,23], synthesis by standard methods [16] and availability from a commercial supplier. Further more, LNAs have great potential to improve capability of nucleic acid recognition [24]. Our laboratory has employed the LNA modified probe to detect target DNA through typical intercalator-based DNA sensors to clear that LNAs posses extraordinarily high affinities for complementary sequences and demonstrate that LNA probes hybridize with very high affinity to perfectly complementary targets, and at the same time the results also show an extraordinary specificity to discriminate the targets that differ by a single base [25].…”

Section: Introductionmentioning

confidence: 97%

A Sandwich‐Type Electrochemical Biosensor for Detection of BCR/ABL Fusion Gene Using Locked Nucleic Acids on Gold Electrode

Wang

Chen

et al. 2009

Electroanalysis

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In this study, a sandwich-type electrochemical enzyme-based LNA-modified DNA biosensor was developed to detect relative gene in chronic Myelogenous Leukemia first. This biosensor is based on a sandwich detection strategy, which involves a pair of probes (a capture probe immobilized at the electrode surface and a reporter probe labeled biotin as an affinity tag for avidin-HRP) modified LNA. Since biotin can be connected with avidin-HRP, this biosensor offers an enzymatically amplified electrochemical current signal for the detection of target DNA. This new pattern exhibits high sensitivity and selectivity, and this biosensor has been used for an assay of PCR real sample with satisfactory result.

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“…[21,22] The furanose conformation of an a-l-LNA monomer is N-type (C3'-endo, 3 E) but it is a DNA mimic as a consequence of the unnatural l configuration. [23] NMR spectroscopic studies as well as molecular modeling simulations of partially and fully modified a-l-LNA:RNA duplexes have shown very similar overall duplex geometry to the corresponding unmodified DNA:RNA duplex, although some local rearrangements of the phosphate backbone were observed to accommodate the unnatural a-l-LNA nucleotides.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Structural Characterization of 2′‐Fluoro‐α‐L‐RNA‐Modified Oligonucleotides

et al. 2011

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We describe the synthesis and binding properties of oligonucleotides that contain one or more 2'-fluoro-α-L-RNA thymine monomer(s). Incorporation of 2'-fluoro-α-L-RNA thymine into oligodeoxynucleotides decreased thermal binding stability slightly upon hybridization with complementary DNA and RNA with the smallest destabilization towards RNA. Thermodynamic data show that the duplex formation with 2'-fluoro-α-L-RNA nucleotides is enthalpically disfavored but entropically favored. 2'-Fluoro-α-L-RNA nucleotides exhibit very good base pairing specificity following Watson--Crick rules. The 2'-fluoro-α-L-RNA monomer was designed as a monocyclic mimic of the bicyclic α-L-LNA, and molecular modeling showed that this indeed is the case as the 2'-fluoro monomer adopts a C3'-endo/C2'-exo sugar pucker. Molecular modeling of modified duplexes show that the 2'-fluoro-α-L-RNA nucleotides partake in Watson--Crick base pairing and nucleobase stacking when incorporated in duplexes while the unnatural α-L-ribo configured geometry of the sugar is absorbed by changes in the sugar-phosphate backbone torsion angles. The duplex behavior of our new nucleotide follows that of α-L-LNA, by and large.

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LNA (LOCKED NUCLEIC ACID) AND THE DIASTEREOISOMERIC Α-L-Lna: CONFORMATIONAL TUNING AND HIGH-AFFINITY RECOGNITION OF DNA/RNA TARGETS

Cited by 61 publications

References 16 publications

Chemistry of locked nucleic acids (LNA): Design, synthesis, and bio-physical properties

Chemistry of locked nucleic acids (LNA): Design, synthesis, and bio-physical properties

A Sandwich‐Type Electrochemical Biosensor for Detection of BCR/ABL Fusion Gene Using Locked Nucleic Acids on Gold Electrode

Synthesis and Structural Characterization of 2′‐Fluoro‐α‐L‐RNA‐Modified Oligonucleotides

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