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Article Abstract
A synthesis of 2'-fluoro and 2'-methoxy N6-methyladenosine phosphoramidites and their successful incorporation into oligonucleotides is reported. 2'-fluoro and 2́-methoxy modifications of sugars in siRNAs are known to aid stability and N6-methylation modifies the potency of therapeutic silencing RNAs (siRNA). We demonstrate that a combination of those modifications incorporated into the antisense strand of siRNA leads to efficient knockdown of a target gene in cells. This work broadens the available pool of chemical modifications of therapeutic siRNAs and provides tools for their efficient synthesis.
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| http://dx.doi.org/10.1016/j.bmcl.2023.129126 | DOI Listing |
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Synthesis of 2'-modified N6-methyladenosine phosphoramidites and their incorporation into siRNA.
Bioorg Med Chem Lett
February 2023
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
A synthesis of 2'-fluoro and 2'-methoxy N6-methyladenosine phosphoramidites and their successful incorporation into oligonucleotides is reported. 2'-fluoro and 2́-methoxy modifications of sugars in siRNAs are known to aid stability and N6-methylation modifies the potency of therapeutic silencing RNAs (siRNA). We demonstrate that a combination of those modifications incorporated into the antisense strand of siRNA leads to efficient knockdown of a target gene in cells.
View Article and Find Full Text PDFImproved Synthesis of Phosphoramidite-Protected -Methyladenosine via BOP-Mediated SAr Reaction.
Molecules
December 2020
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK.
Article Synopsis
- * The authors present an improved five-step synthesis method for creating mA phosphoramidite, using a specific chemical reaction that enhances overall yield significantly.
- * This new synthesis approach not only improves mA production but is also applicable for other adenosine derivatives, including ethanoadenosine, which is relevant for research on the anticancer drug Carmustine.
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March 2019
Department of Chemistry, University of California, One Shields Ave, Davis, CA 95616, USA. Electronic address:
Over 150 unique RNA modifications are now known including several nonstandard nucleotides present in the body of messenger RNAs. These modifications can alter a transcript's function and are collectively referred to as the epitrancriptome. Chemically modified nucleoside analogs are poised to play an important role in the study of these epitranscriptomic marks.
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Nucleic Acids Res
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Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznañ, Poland.
The N6-alkyladenosines and 2-methylthio-N6-alkyladenosines are the most common modified adenosine nucleosides and transfer ribonucleic acids (tRNA) are particularly rich in these modified nucleosides. They are present at position 37 of the anticodon arm and the contribution of these hypermodified nucleosides to codon-anticodon interactions, as well as translation, are significant, although not fully understood. Herein we described a new chemical synthesis method of the oligoribonucleotides containing N6-alkyladenosines and 2-methylthio-N6-alkyladenosines via post-synthetic modifications of precursor oligoribonucleotides.
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Nucleic Acids Res
March 2002
Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
The base moiety of 1-N-methyladenosine can be protected with a chloroacetyl group for incorporation of this modified nucleoside into DNA and RNA. Carefully controlled anhydrous conditions are needed for deprotection of the oligonucleotides.
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