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Quick Access to Nucleobase-Modified Phosphoramidites for the Synthesis of Oligoribonucleotides Containing Post-Transcriptional Modifications and Epitranscriptomic Marks
[Image: see text] Herein, we report a straightforward one-step procedure for modifying N-nucleophilic groups in the nucleobases of commercially available nucleoside phosphoramidites. This method involves the deprotonation of amide groups under phase-transfer conditions and subsequent reaction with e...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9361293/ https://www.ncbi.nlm.nih.gov/pubmed/35857285 http://dx.doi.org/10.1021/acs.joc.2c01390 |
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author | Ziemkiewicz, Kamil Warminski, Marcin Wojcik, Radoslaw Kowalska, Joanna Jemielity, Jacek |
author_facet | Ziemkiewicz, Kamil Warminski, Marcin Wojcik, Radoslaw Kowalska, Joanna Jemielity, Jacek |
author_sort | Ziemkiewicz, Kamil |
collection | PubMed |
description | [Image: see text] Herein, we report a straightforward one-step procedure for modifying N-nucleophilic groups in the nucleobases of commercially available nucleoside phosphoramidites. This method involves the deprotonation of amide groups under phase-transfer conditions and subsequent reaction with electrophilic molecules such as alkyl halides or organic isocyanates. Using this approach, we obtained 10 different classes of modified nucleoside phosphoramidites suitable for the synthesis of oligonucleotides, including several noncanonical nucleotides found in natural RNA or DNA (e.g., m(6)A, i(6)A, m(1)A, g(6)A, m(3)C, m(4)C, m(3)U, m(1)G, and m(2)G). Such modification of nucleobases is a common mechanism for post-transcriptional regulation of RNA stability and translational activity in various organisms. To better understand this process, relevant cellular recognition partners (e.g., proteins) must be identified and characterized. However, this step has been impeded by limited access to molecular tools containing such modified nucleotides. |
format | Online Article Text |
id | pubmed-9361293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-93612932022-08-10 Quick Access to Nucleobase-Modified Phosphoramidites for the Synthesis of Oligoribonucleotides Containing Post-Transcriptional Modifications and Epitranscriptomic Marks Ziemkiewicz, Kamil Warminski, Marcin Wojcik, Radoslaw Kowalska, Joanna Jemielity, Jacek J Org Chem [Image: see text] Herein, we report a straightforward one-step procedure for modifying N-nucleophilic groups in the nucleobases of commercially available nucleoside phosphoramidites. This method involves the deprotonation of amide groups under phase-transfer conditions and subsequent reaction with electrophilic molecules such as alkyl halides or organic isocyanates. Using this approach, we obtained 10 different classes of modified nucleoside phosphoramidites suitable for the synthesis of oligonucleotides, including several noncanonical nucleotides found in natural RNA or DNA (e.g., m(6)A, i(6)A, m(1)A, g(6)A, m(3)C, m(4)C, m(3)U, m(1)G, and m(2)G). Such modification of nucleobases is a common mechanism for post-transcriptional regulation of RNA stability and translational activity in various organisms. To better understand this process, relevant cellular recognition partners (e.g., proteins) must be identified and characterized. However, this step has been impeded by limited access to molecular tools containing such modified nucleotides. American Chemical Society 2022-07-20 2022-08-05 /pmc/articles/PMC9361293/ /pubmed/35857285 http://dx.doi.org/10.1021/acs.joc.2c01390 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Ziemkiewicz, Kamil Warminski, Marcin Wojcik, Radoslaw Kowalska, Joanna Jemielity, Jacek Quick Access to Nucleobase-Modified Phosphoramidites for the Synthesis of Oligoribonucleotides Containing Post-Transcriptional Modifications and Epitranscriptomic Marks |
title | Quick Access to
Nucleobase-Modified Phosphoramidites
for the Synthesis of Oligoribonucleotides Containing Post-Transcriptional
Modifications and Epitranscriptomic Marks |
title_full | Quick Access to
Nucleobase-Modified Phosphoramidites
for the Synthesis of Oligoribonucleotides Containing Post-Transcriptional
Modifications and Epitranscriptomic Marks |
title_fullStr | Quick Access to
Nucleobase-Modified Phosphoramidites
for the Synthesis of Oligoribonucleotides Containing Post-Transcriptional
Modifications and Epitranscriptomic Marks |
title_full_unstemmed | Quick Access to
Nucleobase-Modified Phosphoramidites
for the Synthesis of Oligoribonucleotides Containing Post-Transcriptional
Modifications and Epitranscriptomic Marks |
title_short | Quick Access to
Nucleobase-Modified Phosphoramidites
for the Synthesis of Oligoribonucleotides Containing Post-Transcriptional
Modifications and Epitranscriptomic Marks |
title_sort | quick access to
nucleobase-modified phosphoramidites
for the synthesis of oligoribonucleotides containing post-transcriptional
modifications and epitranscriptomic marks |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9361293/ https://www.ncbi.nlm.nih.gov/pubmed/35857285 http://dx.doi.org/10.1021/acs.joc.2c01390 |
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