Synthesis and Properties of 2′-O,4′-C-Ethylene-Bridged Nucleic Acids (ENA) as Effective Antisense Oligonucleotides.

Morita, Koji; Takagi, M.; Hasegawa, Chikako; Kaneko, Masakatsu; Tsutsumi, Sadami; Sone, Junko; Ishikawa, T.; Imanishi, Takeshi; Koizumi, Makoto

doi:10.1002/chin.200333215

Cited by 33 publications

(98 citation statements)

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“…[28] A uniformly modified ENA PS oligonucleotide, ENA-13, was prepared on an ABI 394 DNA/RNA synthesizer on a 1-µmol scale synthesis. [5,6] To obtain PS bonds, CPG was treated with 0.02 M xanthane hydride in CH 3 CN:pyridine (9:1 v/v) solution for 900 s. After cleavage from the CPG and deprotection by treatment with aqueous ammonia for 5 h at 55 • C, the ENA PS oligonucleotide was purified by a reverse-phase (RP) column (Cosmosil 75C 18 -prep, 30 × 250 mm, Nakalai Tesque, Japan) with a solution of CH 3 CN and 50 mM triethylammonium bicarbonate (pH 7.5). Deprotection of the 4, 4 -dimethoxytrityl group of the oligonucleotide was conducted by treatment with 80% acetic acid for 20 min.…”

Section: Synthesis Of Oligonucleotidesmentioning

confidence: 98%

“…[5,6,27] Ethylene glycol-modified controlled pore grass (CPG) (1) was synthesized according to reported methods. [28] A uniformly modified ENA PS oligonucleotide, ENA-13, was prepared on an ABI 394 DNA/RNA synthesizer on a 1-µmol scale synthesis.…”

Section: Synthesis Of Oligonucleotidesmentioning

confidence: 99%

“…The oligonucleotides with ENA residues exhibit a binding affinity to ssDNA and ssRNA as high as that of 2 ,4 -BNA/LNA and show excellent triplex formation with dsDNA. [5,6,10] The ENA oligonucleotides also exhibit much higher nuclease resistance than the 2 ,4 -BNA/LNA oligonucleotides. [5,6,10] We have shown the intracellular antisense activity of ENA oligonucleotides for vascular endothelial growth factor (VEGF) and organic anion transporting polypeptide (oatp) as targets.…”

Section: Introductionmentioning

confidence: 98%

“…[5,6,10] The ENA oligonucleotides also exhibit much higher nuclease resistance than the 2 ,4 -BNA/LNA oligonucleotides. [5,6,10] We have shown the intracellular antisense activity of ENA oligonucleotides for vascular endothelial growth factor (VEGF) and organic anion transporting polypeptide (oatp) as targets. [11,12] The ENA oligonucleotides could be used for exon skipping to bind dystrophin pre-mRNA and inhibit its splicing reaction; [13,14] therefore, they are considered to be candidates for the next generation of antisense molecules.…”

Section: Introductionmentioning

confidence: 98%

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Comparison Between Properties Of 2′-O,4′-C-Ethylene-Bridged Nucleic Acid (Ena®) Phosphorothioate Oligonucleotides And N3′-P5′ Thiophosphoramidate Oligonucleotides

Horie¹,

Morita²,

Kawakami³

et al. 2006

Nucleosides, Nucleotides & Nucleic Acids

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Synthesis and properties of an oligonucleotide uniformly modified with 2'-O,4-C-ethylene-bridged nucleic acid (ENA) units were compared with those of GRN163, which is modified with N3'-P5' thiophosphoramidates, with the sequence targeting human telomerase RNA subunit. Although an ENA phosphorothioate oligonucleotide, ENA-13, could be synthesized using ENA phosphoramidites on a 100-mg scale, synthesis of GRN163 was very hard even on a 1-micomol scale. In view of both stability of the duplex formation with complementary RNA and the efficiency of cellular uptake by endocytosis, ENA-13 was superior to GRN163. These findings suggest that ENA-13 has useful properties for antisense therapeutic application.

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Section: Synthesis Of Oligonucleotidesmentioning

confidence: 98%

Section: Synthesis Of Oligonucleotidesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Comparison Between Properties Of 2′-O,4′-C-Ethylene-Bridged Nucleic Acid (Ena®) Phosphorothioate Oligonucleotides And N3′-P5′ Thiophosphoramidate Oligonucleotides

Horie¹,

Morita²,

Kawakami³

et al. 2006

Nucleosides, Nucleotides & Nucleic Acids

Self Cite

View full text Add to dashboard Cite

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“…The popular way to constrain the flexible pentose sugar moiety is linking two endocylic sugar carbons by a short covalent linkage. 11 Thus, BNA/LNA, [12][13][14][15] ENA [16][17][18][19] and their analoges [20][21][22][23] were obtained by a covalent bond formation between C2′…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Structure of New Methylene-Bridged Hexopyranosyl Nucleoside (BHNA)

Zhou¹,

Plashkevych²,

Liu³

et al. 2009

HETEROCYCLES

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-A new member of hexopyranosyl nucleoside family, methylene-bridged hexopyranosyl nucleoside (BHNA), has been synthesized through generation of carbon radical at C6′ in [6′S-Me, 7′S-Me]-carba-LNA T nucleoside, followed by rearrangement to C4′ radical which was quenched by hydrogen atom to give BHNA. The stereoelectronic requirement for this unusual radical rearrangement has been elucidated by chemical model building and ab intio calculations to show that the coplanarity of the single electron occupied p-orbital at C6' with σ* O4'-C4' plays an important role for the rearrangement reaction to take place. The solution structure of BHNA has also been studied using NMR as well as by ab initio calculations. The new six-membered pyranosyl ring in BHNA, unlike other known hexopyranosyl nucleosides, adopts a twist conformation, with base moiety occupying the axial position while 3′-hydroxymethyl and 4′-hydroxyl occupying the equatorial position.

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Incorporation of Pseudo‐complementary Bases 2,6‐Diaminopurine and 2‐Thiouracil into Serinol Nucleic Acid (SNA) to Promote SNA/RNA Hybridization

Sato

Murayama

Kodama

et al. 2020

Chemistry An Asian Journal

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Serinol nucleic acid (SNA) is a promising candidate for nucleic acid-based molecular probes and drugs due to its high affinity for RNA. Our previous work revealed that incorporation of 2,6-diaminpurine (D), which can form three hydrogen bonds with uracil, into SNA increases the melting temperature of SNA-RNA duplexes. However, D incorporation into short self-complementary regions of SNA promoted self-dimerization and hindered hybridization with RNA. Here we synthesized a SNA monomer of 2thiouracil (sU), which was expected to inhibit base pairing with D by steric hindrance between sulfur and the amino group. To prepare the SNA containing D and sU in high yield, we customized the protecting groups on D and sU monomers that can be readily deprotected under acidic conditions. Incorporation of D and sU into SNA facilitated stable duplex formation with target RNA by suppressing the self-hybridization of SNA and increasing the stability of the heteroduplex of SNA and its complementary RNA. Our results have important implications for the development of SNA-based probes and nucleic acid drugs.[a] Dr.

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Synthesis and Properties of 2′-O,4′-C-Ethylene-Bridged Nucleic Acids (ENA) as Effective Antisense Oligonucleotides.

Cited by 33 publications

References 1 publication

Comparison Between Properties Of 2′-O,4′-C-Ethylene-Bridged Nucleic Acid (Ena®) Phosphorothioate Oligonucleotides And N3′-P5′ Thiophosphoramidate Oligonucleotides

Comparison Between Properties Of 2′-O,4′-C-Ethylene-Bridged Nucleic Acid (Ena®) Phosphorothioate Oligonucleotides And N3′-P5′ Thiophosphoramidate Oligonucleotides

Synthesis and Structure of New Methylene-Bridged Hexopyranosyl Nucleoside (BHNA)

Incorporation of Pseudo‐complementary Bases 2,6‐Diaminopurine and 2‐Thiouracil into Serinol Nucleic Acid (SNA) to Promote SNA/RNA Hybridization

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