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Conjugation of chemical handles and functional moieties to DNA during solid phase synthesis with sulfonyl azides

Labelling of oligonucleotides with dyes, targeting ligands, and other moieties has become ever more essential in life-sciences. Conventionally, modifications are introduced to oligonucleotides during solid phase synthesis by special phosphoramidites functionalised with a chemical handle or the desir...

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Autores principales: Santorelli, Angel, Gothelf, Kurt V
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303310/
https://www.ncbi.nlm.nih.gov/pubmed/35801866
http://dx.doi.org/10.1093/nar/gkac566
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author Santorelli, Angel
Gothelf, Kurt V
author_facet Santorelli, Angel
Gothelf, Kurt V
author_sort Santorelli, Angel
collection PubMed
description Labelling of oligonucleotides with dyes, targeting ligands, and other moieties has become ever more essential in life-sciences. Conventionally, modifications are introduced to oligonucleotides during solid phase synthesis by special phosphoramidites functionalised with a chemical handle or the desired functional group. In this work, we present a facile and inexpensive method to introduce modifications to oligonucleotides without the need for special phosphoramidites. Sulfonyl azides are applied to react with one or more selected phosphite intermediates during solid phase synthesis. We have prepared 11 sulfonyl azides with different chemical handles such as amine, azide, alkyne, and thiol, and we have further introduced functionalities such as pyrene, other dyes, photo-switchable azobenzenes, and a steroid. The method is compatible with current phosphoramidite-based automated oligonucleotide synthesis and serves as a simple alternative to the unstable and expensive special phosphoramidites currently used for conjugation to oligonucleotides.
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spelling pubmed-93033102022-07-22 Conjugation of chemical handles and functional moieties to DNA during solid phase synthesis with sulfonyl azides Santorelli, Angel Gothelf, Kurt V Nucleic Acids Res Chemical Biology and Nucleic Acid Chemistry Labelling of oligonucleotides with dyes, targeting ligands, and other moieties has become ever more essential in life-sciences. Conventionally, modifications are introduced to oligonucleotides during solid phase synthesis by special phosphoramidites functionalised with a chemical handle or the desired functional group. In this work, we present a facile and inexpensive method to introduce modifications to oligonucleotides without the need for special phosphoramidites. Sulfonyl azides are applied to react with one or more selected phosphite intermediates during solid phase synthesis. We have prepared 11 sulfonyl azides with different chemical handles such as amine, azide, alkyne, and thiol, and we have further introduced functionalities such as pyrene, other dyes, photo-switchable azobenzenes, and a steroid. The method is compatible with current phosphoramidite-based automated oligonucleotide synthesis and serves as a simple alternative to the unstable and expensive special phosphoramidites currently used for conjugation to oligonucleotides. Oxford University Press 2022-07-08 /pmc/articles/PMC9303310/ /pubmed/35801866 http://dx.doi.org/10.1093/nar/gkac566 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemical Biology and Nucleic Acid Chemistry
Santorelli, Angel
Gothelf, Kurt V
Conjugation of chemical handles and functional moieties to DNA during solid phase synthesis with sulfonyl azides
title Conjugation of chemical handles and functional moieties to DNA during solid phase synthesis with sulfonyl azides
title_full Conjugation of chemical handles and functional moieties to DNA during solid phase synthesis with sulfonyl azides
title_fullStr Conjugation of chemical handles and functional moieties to DNA during solid phase synthesis with sulfonyl azides
title_full_unstemmed Conjugation of chemical handles and functional moieties to DNA during solid phase synthesis with sulfonyl azides
title_short Conjugation of chemical handles and functional moieties to DNA during solid phase synthesis with sulfonyl azides
title_sort conjugation of chemical handles and functional moieties to dna during solid phase synthesis with sulfonyl azides
topic Chemical Biology and Nucleic Acid Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303310/
https://www.ncbi.nlm.nih.gov/pubmed/35801866
http://dx.doi.org/10.1093/nar/gkac566
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