Chemical Synthesis of the Antiviral Nucleotide Analogue ddhCTP
3'-Deoxy-3',4'-didehydro-cytidine triphosphate (ddhCTP) is a novel antiviral molecule produced by the enzyme viperin as part of the innate immune response. ddhCTP has been shown to act as an obligate chain terminator of flavivirus and SARS-CoV-2 RNA-dependent RNA polymerases; however, further biophysical studies have been precluded by limited access to this promising antiviral. Herein, we report a robust and scalable synthesis of ddhCTP as well as the mono- and diphosphates ddhCMP and ddhCDP, respectively. Identification of a 2'-silyl ether protection strategy enabled selective synthesis and facile purification of the 5'-triphosphate, culminating in the preparation of ddhCTP on a gram scale.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:86 |
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| Enthalten in: |
The Journal of organic chemistry - 86(2021), 13 vom: 02. Juli, Seite 8843-8850 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wood, James M [VerfasserIn] |
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| Links: |
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| Themen: |
65-47-4 |
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| Anmerkungen: |
Date Completed 12.07.2021 Date Revised 10.09.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.joc.1c00761 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM326738649 |
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| 245 | 1 | 0 | |a Chemical Synthesis of the Antiviral Nucleotide Analogue ddhCTP |
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| 500 | |a Date Revised 10.09.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 3'-Deoxy-3',4'-didehydro-cytidine triphosphate (ddhCTP) is a novel antiviral molecule produced by the enzyme viperin as part of the innate immune response. ddhCTP has been shown to act as an obligate chain terminator of flavivirus and SARS-CoV-2 RNA-dependent RNA polymerases; however, further biophysical studies have been precluded by limited access to this promising antiviral. Herein, we report a robust and scalable synthesis of ddhCTP as well as the mono- and diphosphates ddhCMP and ddhCDP, respectively. Identification of a 2'-silyl ether protection strategy enabled selective synthesis and facile purification of the 5'-triphosphate, culminating in the preparation of ddhCTP on a gram scale | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Proteins |2 NLM | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 650 | 7 | |a Cytidine Triphosphate |2 NLM | |
| 650 | 7 | |a 65-47-4 |2 NLM | |
| 700 | 1 | |a Evans, Gary B |e verfasserin |4 aut | |
| 700 | 1 | |a Grove, Tyler L |e verfasserin |4 aut | |
| 700 | 1 | |a Almo, Steven C |e verfasserin |4 aut | |
| 700 | 1 | |a Cameron, Scott A |e verfasserin |4 aut | |
| 700 | 1 | |a Furneaux, Richard H |e verfasserin |4 aut | |
| 700 | 1 | |a Harris, Lawrence D |e verfasserin |4 aut | |
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