Abstract
The rationale for a pronucleotide approach based on the use of phosphotriesters which incorporate enzyme-mediated bio-labile protection is discussed in detail. Among the studied bio-labile phosphate protecting groups, the S-acyl-2-thioethyl (SATE) groups appeared the most promising as exemplified in cell culture systems in the case of the pronucleotides of 3'-azido-3'-deoxythymidine, 2',3'-didehydro-3'-deoxythymidine, 2',3'-dideoxyadenosine and acyclovir In vivo implementations of such bis(SATE) pronucleotides have been planned for future animal studies.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Acyclovir / analogs & derivatives
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Animals
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / chemistry
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Antiviral Agents / metabolism
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Drug Design
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Humans
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Indicators and Reagents
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Models, Biological
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Nucleotides / chemical synthesis*
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Nucleotides / chemistry
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Nucleotides / metabolism
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / metabolism
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Structure-Activity Relationship
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Zidovudine / analogs & derivatives
Substances
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Antiviral Agents
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Indicators and Reagents
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Nucleotides
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Prodrugs
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Zidovudine
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Acyclovir