Alpha-carboxynucleoside phosphonates : direct-acting inhibitors of viral DNA polymerases
Acyclic nucleoside phosphonates represent a well-defined class of clinically used nucleoside analogs. All acyclic nucleoside phosphonates need intracellular phosphorylation before they can bind viral DNA polymerases. Recently, a novel class of alpha-carboxynucleoside phosphonates have been designed to mimic the natural 2'-deoxynucleotide 5'-triphosphate substrates of DNA polymerases. They contain a carboxyl group in the phosphonate moiety linked to the nucleobase through a cyclic or acyclic bridge. Alpha-carboxynucleoside phosphonates act as viral DNA polymerase inhibitors without any prior requirement of metabolic conversion. Selective inhibitory activity against retroviral reverse transcriptase and herpesvirus DNA polymerases have been demonstrated. These compounds have a unique mechanism of inhibition of viral DNA polymerases, and provide possibilities for further modifications to optimize and fine tune their antiviral DNA polymerase spectrum.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Future medicinal chemistry - 11(2019), 2 vom: 01. Jan., Seite 137-154 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Balzarini, Jan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.08.2019 Date Revised 19.05.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2018-0324 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM292768559 |
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| 245 | 1 | 0 | |a Alpha-carboxynucleoside phosphonates |b direct-acting inhibitors of viral DNA polymerases |
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| 500 | |a Date Completed 08.08.2019 | ||
| 500 | |a Date Revised 19.05.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Acyclic nucleoside phosphonates represent a well-defined class of clinically used nucleoside analogs. All acyclic nucleoside phosphonates need intracellular phosphorylation before they can bind viral DNA polymerases. Recently, a novel class of alpha-carboxynucleoside phosphonates have been designed to mimic the natural 2'-deoxynucleotide 5'-triphosphate substrates of DNA polymerases. They contain a carboxyl group in the phosphonate moiety linked to the nucleobase through a cyclic or acyclic bridge. Alpha-carboxynucleoside phosphonates act as viral DNA polymerase inhibitors without any prior requirement of metabolic conversion. Selective inhibitory activity against retroviral reverse transcriptase and herpesvirus DNA polymerases have been demonstrated. These compounds have a unique mechanism of inhibition of viral DNA polymerases, and provide possibilities for further modifications to optimize and fine tune their antiviral DNA polymerase spectrum | ||
| 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 | 4 | |a Review | |
| 650 | 4 | |a HIV | |
| 650 | 4 | |a acyclic nucleoside phosphonate (ANP) | |
| 650 | 4 | |a chemotherapeutics | |
| 650 | 4 | |a herpesviruses | |
| 650 | 4 | |a nucleoside-analog inhibitor | |
| 650 | 4 | |a reverse transcriptase (RT) | |
| 650 | 4 | |a viral DNA polymerase | |
| 650 | 4 | |a α-carboxynucleoside phosphonate (α-CNP) | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Nucleic Acid Synthesis Inhibitors |2 NLM | |
| 650 | 7 | |a Nucleosides |2 NLM | |
| 650 | 7 | |a Organophosphonates |2 NLM | |
| 650 | 7 | |a Reverse Transcriptase Inhibitors |2 NLM | |
| 650 | 7 | |a Viral Proteins |2 NLM | |
| 650 | 7 | |a DNA-Directed DNA Polymerase |2 NLM | |
| 650 | 7 | |a EC 2.7.7.7 |2 NLM | |
| 650 | 7 | |a Exodeoxyribonucleases |2 NLM | |
| 650 | 7 | |a EC 3.1.- |2 NLM | |
| 650 | 7 | |a DNA polymerase, Simplexvirus |2 NLM | |
| 650 | 7 | |a EC 3.1.11.- |2 NLM | |
| 700 | 1 | |a Ford, Alan |e verfasserin |4 aut | |
| 700 | 1 | |a Maguire, Nuala M |e verfasserin |4 aut | |
| 700 | 1 | |a John, Jubi |e verfasserin |4 aut | |
| 700 | 1 | |a Das, Kalyan |e verfasserin |4 aut | |
| 700 | 1 | |a Arnold, Eddy |e verfasserin |4 aut | |
| 700 | 1 | |a Dehaen, Wim |e verfasserin |4 aut | |
| 700 | 1 | |a Maguire, Anita |e verfasserin |4 aut | |
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