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N2 modified cap analogues as translation inhibitors and substrates for preparation of therapeutic mRNA
In recent years many scientists have begun to focus on the mRNA molecule’s emeregence as a new type of drug. Its fast-moving and successful career as a vaccine technology cannot be underestimated. mRNA provides new opportunities and allows for the rapid preparation of effective drugs at low cost. Th...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618310/ https://www.ncbi.nlm.nih.gov/pubmed/37656232 http://dx.doi.org/10.1007/s00249-023-01676-7 |
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author | Kurpiejewski, Karol Jankowska-Anyszka, Marzena Grzela, Renata |
author_facet | Kurpiejewski, Karol Jankowska-Anyszka, Marzena Grzela, Renata |
author_sort | Kurpiejewski, Karol |
collection | PubMed |
description | In recent years many scientists have begun to focus on the mRNA molecule’s emeregence as a new type of drug. Its fast-moving and successful career as a vaccine technology cannot be underestimated. mRNA provides new opportunities and allows for the rapid preparation of effective drugs at low cost. These extensive possibilities stem from a number of factors, but the small cap structure located at the 5′ end of the mRNA is one contributing factor. Cap protects mRNA and ensures efficient recruitment to the biosynthesis machinery. Furthermore, it allows for the easy introduction of various modifications that influence the activity of the entire mRNA. Among the many different cap analogues that have been reported, those modified at the N2 position of guanosine have been systematically developed. N2-modified caps in the form of nucleoside monophosphates or dinucleotides show favorable biological properties, as well as a high capacity to inhibit the translation process in the cell-free RRL system. Modified N2 dinucleotides are efficiently incorporated into the structure of the mRNA transcript, and in specific circumstances with the correct orientation, making them an interesting alternative for ARCA-type analogues. Moreover, mRNA transcripts containing cap structures modified within the exocyclic amino group show very high translational activity. Therefore, analogues modified at the N2 position may have future applications as therapeutics against various manifestations of cancer and as desirable tools in RNA engineering. |
format | Online Article Text |
id | pubmed-10618310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-106183102023-11-02 N2 modified cap analogues as translation inhibitors and substrates for preparation of therapeutic mRNA Kurpiejewski, Karol Jankowska-Anyszka, Marzena Grzela, Renata Eur Biophys J Review In recent years many scientists have begun to focus on the mRNA molecule’s emeregence as a new type of drug. Its fast-moving and successful career as a vaccine technology cannot be underestimated. mRNA provides new opportunities and allows for the rapid preparation of effective drugs at low cost. These extensive possibilities stem from a number of factors, but the small cap structure located at the 5′ end of the mRNA is one contributing factor. Cap protects mRNA and ensures efficient recruitment to the biosynthesis machinery. Furthermore, it allows for the easy introduction of various modifications that influence the activity of the entire mRNA. Among the many different cap analogues that have been reported, those modified at the N2 position of guanosine have been systematically developed. N2-modified caps in the form of nucleoside monophosphates or dinucleotides show favorable biological properties, as well as a high capacity to inhibit the translation process in the cell-free RRL system. Modified N2 dinucleotides are efficiently incorporated into the structure of the mRNA transcript, and in specific circumstances with the correct orientation, making them an interesting alternative for ARCA-type analogues. Moreover, mRNA transcripts containing cap structures modified within the exocyclic amino group show very high translational activity. Therefore, analogues modified at the N2 position may have future applications as therapeutics against various manifestations of cancer and as desirable tools in RNA engineering. Springer International Publishing 2023-09-01 2023 /pmc/articles/PMC10618310/ /pubmed/37656232 http://dx.doi.org/10.1007/s00249-023-01676-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Kurpiejewski, Karol Jankowska-Anyszka, Marzena Grzela, Renata N2 modified cap analogues as translation inhibitors and substrates for preparation of therapeutic mRNA |
title | N2 modified cap analogues as translation inhibitors and substrates for preparation of therapeutic mRNA |
title_full | N2 modified cap analogues as translation inhibitors and substrates for preparation of therapeutic mRNA |
title_fullStr | N2 modified cap analogues as translation inhibitors and substrates for preparation of therapeutic mRNA |
title_full_unstemmed | N2 modified cap analogues as translation inhibitors and substrates for preparation of therapeutic mRNA |
title_short | N2 modified cap analogues as translation inhibitors and substrates for preparation of therapeutic mRNA |
title_sort | n2 modified cap analogues as translation inhibitors and substrates for preparation of therapeutic mrna |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618310/ https://www.ncbi.nlm.nih.gov/pubmed/37656232 http://dx.doi.org/10.1007/s00249-023-01676-7 |
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