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Stereoselective RNA reaction with chiral 2′-OH acylating agents
The reactivity of RNA 2′-OH groups with acylating agents has recently been investigated for high-yield conjugation of RNA strands. To date, only achiral molecules have been studied for this reaction, despite the complex chiral structure of RNA. Here we prepare a set of chiral acylimidazoles and stud...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664579/ https://www.ncbi.nlm.nih.gov/pubmed/38023505 http://dx.doi.org/10.1039/d3sc03067a |
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author | Shioi, Ryuta Xiao, Lu Chatterjee, Sayantan Kool, Eric T. |
author_facet | Shioi, Ryuta Xiao, Lu Chatterjee, Sayantan Kool, Eric T. |
author_sort | Shioi, Ryuta |
collection | PubMed |
description | The reactivity of RNA 2′-OH groups with acylating agents has recently been investigated for high-yield conjugation of RNA strands. To date, only achiral molecules have been studied for this reaction, despite the complex chiral structure of RNA. Here we prepare a set of chiral acylimidazoles and study their stereoselectivity in RNA reactions. Reactions performed with unfolded and folded RNAs reveal that positional selectivity and reactivity vary widely with local RNA macro-chirality. We further document remarkable effects of chirality on reagent reactivity, identifying an asymmetric reagent with 1000-fold greater reactivity than prior achiral reagents. In addition, we identify a chiral compound with higher RNA structural selectivity than any previously reported RNA-mapping species. Further, azide-containing homologs of a chiral dimethylalanine reagent were synthesized and applied to local RNA labeling, displaying 92% yield and 16 : 1 diastereoselectivity. The results establish that reagent stereochemistry and chiral RNA structure are critical elements of small molecule-RNA reactions, and demonstrate new chemical strategies for selective RNA modification and probing. |
format | Online Article Text |
id | pubmed-10664579 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-106645792023-11-07 Stereoselective RNA reaction with chiral 2′-OH acylating agents Shioi, Ryuta Xiao, Lu Chatterjee, Sayantan Kool, Eric T. Chem Sci Chemistry The reactivity of RNA 2′-OH groups with acylating agents has recently been investigated for high-yield conjugation of RNA strands. To date, only achiral molecules have been studied for this reaction, despite the complex chiral structure of RNA. Here we prepare a set of chiral acylimidazoles and study their stereoselectivity in RNA reactions. Reactions performed with unfolded and folded RNAs reveal that positional selectivity and reactivity vary widely with local RNA macro-chirality. We further document remarkable effects of chirality on reagent reactivity, identifying an asymmetric reagent with 1000-fold greater reactivity than prior achiral reagents. In addition, we identify a chiral compound with higher RNA structural selectivity than any previously reported RNA-mapping species. Further, azide-containing homologs of a chiral dimethylalanine reagent were synthesized and applied to local RNA labeling, displaying 92% yield and 16 : 1 diastereoselectivity. The results establish that reagent stereochemistry and chiral RNA structure are critical elements of small molecule-RNA reactions, and demonstrate new chemical strategies for selective RNA modification and probing. The Royal Society of Chemistry 2023-11-07 /pmc/articles/PMC10664579/ /pubmed/38023505 http://dx.doi.org/10.1039/d3sc03067a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Shioi, Ryuta Xiao, Lu Chatterjee, Sayantan Kool, Eric T. Stereoselective RNA reaction with chiral 2′-OH acylating agents |
title | Stereoselective RNA reaction with chiral 2′-OH acylating agents |
title_full | Stereoselective RNA reaction with chiral 2′-OH acylating agents |
title_fullStr | Stereoselective RNA reaction with chiral 2′-OH acylating agents |
title_full_unstemmed | Stereoselective RNA reaction with chiral 2′-OH acylating agents |
title_short | Stereoselective RNA reaction with chiral 2′-OH acylating agents |
title_sort | stereoselective rna reaction with chiral 2′-oh acylating agents |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664579/ https://www.ncbi.nlm.nih.gov/pubmed/38023505 http://dx.doi.org/10.1039/d3sc03067a |
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