Abstract
The use of small molecule inhibitors in the study of cellular processes is a powerful approach to understanding gene function. During the course of a high throughput screen for novel inhibitors of eukaryotic translation, we identified a number of nucleic acid binding ligands that showed activity in our assay. When tested on a panel of mRNA transcripts displaying different modes of translation initiation, these ligands showed a range of biological activities--with some inhibiting both cap-dependent and internal initiation and others preferentially blocking internal initiation. We used this information to identify a novel threading intercalator that inhibits Hepatitis C virus internal initiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acridines / chemistry
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Acriflavine / chemistry
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Acriflavine / pharmacology
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Antiviral Agents / chemistry
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Antiviral Agents / isolation & purification
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Antiviral Agents / pharmacology*
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Hepacivirus / drug effects*
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Humans
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Intercalating Agents / pharmacology*
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Ligands
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Peptidyl Transferases / antagonists & inhibitors
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Protein Biosynthesis / drug effects*
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Protein Synthesis Inhibitors / chemistry
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Protein Synthesis Inhibitors / metabolism
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Protein Synthesis Inhibitors / pharmacology*
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Ribosomes / drug effects
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Ribosomes / metabolism
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Structure-Activity Relationship
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Viral Proteins / biosynthesis
Substances
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Acridines
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Antiviral Agents
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Intercalating Agents
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Ligands
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Protein Synthesis Inhibitors
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Viral Proteins
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Acriflavine
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Peptidyl Transferases