A Chemical Strategy for Intracellular Arming of an Endogenous Broad-Spectrum Antiviral Nucleotide.
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ABSTRACT:
SUBMITTER: Passow KT
PROVIDER: S-EPMC8877721 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
A Chemical Strategy for Intracellular Arming of an Endogenous Broad-Spectrum Antiviral Nucleotide.
Passow Kellan T KT Caldwell Haley S HS Ngo Kiet A KA Arnold Jamie J JJ Antczak Nicole M NM Narayanan Anoop A Jose Joyce J Sturla Shana J SJ Cameron Craig E CE Ciota Alexander T AT Harki Daniel A DA
Journal of medicinal chemistry 20211018 20
The naturally occurring nucleotide 3'-deoxy-3',4'-didehydro-cytidine-5'-triphosphate (<b>ddhCTP</b>) was recently found to exert potent and broad-spectrum antiviral activity. However, nucleoside 5'-triphosphates in general are not cell-permeable, which precludes the direct use of <b>ddhCTP</b> as a therapeutic. To harness the therapeutic potential of this endogenous antiviral nucleotide, we synthesized phosphoramidate prodrug HLB-0532247 (<b>1</b>) and found it to result in dramatically elevated ...[more]
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