Late-stage guanine C8–H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reaction
Abstract Chemically modified nucleosi(ti)des and functional oligonucleotides (ONs, including therapeutic oligonucleotides, aptamer, nuclease, etc.) have been identified playing an essential role in the areas of medicinal chemistry, chemical biology, biotechnology, and nanotechnology. Introduction of...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46671-4 |
| _version_ | 1797247151156232192 |
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| author | Ruoqian Xie Wanlu Li Yuhua Ge Yutong Zhou Guolan Xiao Qin Zhao Yunxi Han Yangyan Li Gang Chen |
| author_facet | Ruoqian Xie Wanlu Li Yuhua Ge Yutong Zhou Guolan Xiao Qin Zhao Yunxi Han Yangyan Li Gang Chen |
| author_sort | Ruoqian Xie |
| collection | DOAJ |
| description | Abstract Chemically modified nucleosi(ti)des and functional oligonucleotides (ONs, including therapeutic oligonucleotides, aptamer, nuclease, etc.) have been identified playing an essential role in the areas of medicinal chemistry, chemical biology, biotechnology, and nanotechnology. Introduction of functional groups into the nucleobases of ONs mostly relies on the laborious de novo chemical synthesis. Due to the importance of nucleosides modification and aforementioned limitations of functionalizing ONs, herein, we describe a highly efficient site-selective alkylation at the C8-position of guanines in guanosine (together with its analogues), GMP, GDP, and GTP, as well as late-stage functionalization of dinucleotides and single-strand ONs (including ssDNA and RNA) through photo-mediated Minisci reaction. Addition of catechol to assist the formation of alkyl radicals via in situ generated boronic acid catechol ester derivatives (BACED) markedly enhances the yields especially for the reaction of less stable primary alkyl radicals, and is the key to success for the post-synthetic alkylation of ONs. This method features excellent chemoselectivity, no necessity for pre-protection, wide range of substrate scope, various free radical precursors, and little strand lesion. Downstream applications in disease treatment and diagnosis, or as biochemical probes to study biological processes after linking with suitable fluorescent compounds are expected. |
| first_indexed | 2024-04-24T19:54:08Z |
| format | Article |
| id | doaj.art-afefdf79f32e446a97b557179516f069 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T19:54:08Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-afefdf79f32e446a97b557179516f0692024-03-24T12:26:48ZengNature PortfolioNature Communications2041-17232024-03-0115111410.1038/s41467-024-46671-4Late-stage guanine C8–H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reactionRuoqian Xie0Wanlu Li1Yuhua Ge2Yutong Zhou3Guolan Xiao4Qin Zhao5Yunxi Han6Yangyan Li7Gang Chen8School of Chemistry and Chemical Engineering, Southeast UniversitySchool of Chemistry and Chemical Engineering, Southeast UniversitySchool of Chemistry and Chemical Engineering, Southeast UniversityShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong UniversityShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong UniversityShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong UniversityShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong UniversityShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong UniversityShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong UniversityAbstract Chemically modified nucleosi(ti)des and functional oligonucleotides (ONs, including therapeutic oligonucleotides, aptamer, nuclease, etc.) have been identified playing an essential role in the areas of medicinal chemistry, chemical biology, biotechnology, and nanotechnology. Introduction of functional groups into the nucleobases of ONs mostly relies on the laborious de novo chemical synthesis. Due to the importance of nucleosides modification and aforementioned limitations of functionalizing ONs, herein, we describe a highly efficient site-selective alkylation at the C8-position of guanines in guanosine (together with its analogues), GMP, GDP, and GTP, as well as late-stage functionalization of dinucleotides and single-strand ONs (including ssDNA and RNA) through photo-mediated Minisci reaction. Addition of catechol to assist the formation of alkyl radicals via in situ generated boronic acid catechol ester derivatives (BACED) markedly enhances the yields especially for the reaction of less stable primary alkyl radicals, and is the key to success for the post-synthetic alkylation of ONs. This method features excellent chemoselectivity, no necessity for pre-protection, wide range of substrate scope, various free radical precursors, and little strand lesion. Downstream applications in disease treatment and diagnosis, or as biochemical probes to study biological processes after linking with suitable fluorescent compounds are expected.https://doi.org/10.1038/s41467-024-46671-4 |
| spellingShingle | Ruoqian Xie Wanlu Li Yuhua Ge Yutong Zhou Guolan Xiao Qin Zhao Yunxi Han Yangyan Li Gang Chen Late-stage guanine C8–H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reaction Nature Communications |
| title | Late-stage guanine C8–H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reaction |
| title_full | Late-stage guanine C8–H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reaction |
| title_fullStr | Late-stage guanine C8–H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reaction |
| title_full_unstemmed | Late-stage guanine C8–H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reaction |
| title_short | Late-stage guanine C8–H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reaction |
| title_sort | late stage guanine c8 h alkylation of nucleosides nucleotides and oligonucleotides via photo mediated minisci reaction |
| url | https://doi.org/10.1038/s41467-024-46671-4 |
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