A Novel Universal Linker for Efficient Synthesis of Phosphorothioate Oligonucleotides

Wang, Zhiwei; Olsen, Phil; Ravikumar, Vasulinga T.

doi:10.1080/15257770701257277

Cited by 11 publications

(3 citation statements)

References 36 publications

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“…A solution of phenylacetyl disulfide in 3-picoline and acetonitrile (1:1 v/v) was used as sulfurizing reagent. “UnyLinker” solid support , was used for the synthesis of ASOs. It has been reported that during the deprotection, oligonucleotide phosphodiseters were released 1.2−1.7 times more quickly than the corresponding phosphorothioates from “UnyLinker” solid support .…”

Section: Antisense Oligonucleotidesmentioning

confidence: 99%

Antisense Oligonucleotides Containing Conformationally Constrained 2′,4′-(N-Methoxy)aminomethylene and 2′,4′-Aminooxymethylene and 2′-O,4′-C-Aminomethylene Bridged Nucleoside Analogues Show Improved Potency in Animal Models

et al. 2010

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To identify chemistries and strategies to improve the potency of MOE second generation ASOs, we have evaluated gapmer antisense oligonucleotides containing BNAs having N-O bonds. These modifications include N-MeO-amino BNA, N-Me-aminooxy BNA, 2',4'-BNA(NC)[NMe], and 2',4'-BNA(NC) bridged nucleoside analogues. These modifications provided increased thermal stability and improved in vitro activity compared to the corresponding ASO containing the MOE modification. Additionally, ASOs containing N-MeO-amino BNA, N-Me-aminooxy BNA, and 2',4'-BNA(NC)[NMe] modifications showed improved in vivo activity (>5-fold) compared to MOE ASO. Importantly, toxicity parameters, such as AST, ALT, liver, kidney, and body weights, were found to be normal for N-MeO-amino BNA, N-Me-aminooxy BNA, and 2',4'-BNA(NC)[NMe] ASO treated animals. The data generated in these experiments suggest that N-MeO-amino BNA, N-Me-aminooxy BNA, and 2',4'-BNA(NC)[NMe] are useful modifications for applications in both antisense and other oligonucleotide based drug discovery efforts.

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Section: Antisense Oligonucleotidesmentioning

confidence: 99%

Antisense Oligonucleotides Containing Conformationally Constrained 2′,4′-(N-Methoxy)aminomethylene and 2′,4′-Aminooxymethylene and 2′-O,4′-C-Aminomethylene Bridged Nucleoside Analogues Show Improved Potency in Animal Models

et al. 2010

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“…In a typical experiment, oligonucleotide synthesis starts on universal linker-derivatized controlled porous glass beads (15). During operation, appropriate reagents are driven by pressure into binary trees that precede the reaction columns.…”

Section: Resultsmentioning

confidence: 99%

A microfluidic oligonucleotide synthesizer

Lee

Snyder

Quake

2010

Nucleic Acids Research

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De novo gene and genome synthesis enables the design of any sequence without the requirement of a pre-existing template as in traditional genetic engineering methods. The ability to mass produce synthetic genes holds great potential for biological research, but widespread availability of de novo DNA constructs is currently hampered by their high cost. In this work, we describe a microfluidic platform for parallel solid phase synthesis of oligonucleotides that can greatly reduce the cost of gene synthesis by reducing reagent consumption (by 100-fold) while maintaining a ∼100 pmol synthesis scale so there is no need for amplification before assembly. Sixteen oligonucleotides were synthesized in parallel on this platform and then successfully used in a ligation-mediated assembly method to generate DNA constructs ∼200 bp in length.

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“…The modified oligonucleotides were synthesized on universal solid support. [14,15] A 0.1 M solution of phosphoramidite 6 was used for the incorporation of 2-O-Me-s 2 U residues. Twelve equivalents of phosphoramidite solutions were delivered in two portions, each followed by a 6 minutes coupling wait time.…”

Section: Synthesis Of Oligonucleotides 7-15mentioning

confidence: 99%

Activity of siRNAs with 2-Thio-2′-O-Methyluridine Modification in Mammalian Cells

Prakash

Naik

Sioufi

et al. 2009

Nucleosides, Nucleotides and Nucleic Acids

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A Novel Universal Linker for Efficient Synthesis of Phosphorothioate Oligonucleotides

Cited by 11 publications

References 36 publications

Antisense Oligonucleotides Containing Conformationally Constrained 2′,4′-(N-Methoxy)aminomethylene and 2′,4′-Aminooxymethylene and 2′-O,4′-C-Aminomethylene Bridged Nucleoside Analogues Show Improved Potency in Animal Models

Antisense Oligonucleotides Containing Conformationally Constrained 2′,4′-(N-Methoxy)aminomethylene and 2′,4′-Aminooxymethylene and 2′-O,4′-C-Aminomethylene Bridged Nucleoside Analogues Show Improved Potency in Animal Models

A microfluidic oligonucleotide synthesizer

Activity of siRNAs with 2-Thio-2′-O-Methyluridine Modification in Mammalian Cells

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