Abstract
We describe the use of organosilanes as inhibitors and structural probes of a membrane protein, the M2 proton channel from influenza A virus. Organosilane amine inhibitors were found to be generally as potent as their carbon analogues in targeting WT A/M2 and more potent against the drug-resistant A/M2-V27A mutant. In addition, intermolecular NOESY spectra with dimethyl-substituted organosilane amine inhibitors clearly located the drug binding site at the N-terminal lumen of the A/M2 channel close to V27.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amines / chemistry
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Amines / pharmacology
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology*
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Binding Sites
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Drug Resistance, Viral
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Humans
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Influenza A virus / drug effects*
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Influenza A virus / genetics
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Influenza, Human / drug therapy
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Models, Molecular
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Mutation
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Proton Pump Inhibitors / chemistry
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Proton Pump Inhibitors / pharmacology*
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Proton Pumps / genetics
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Proton Pumps / metabolism*
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Silanes / chemistry
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Silanes / pharmacology*
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Viral Proteins / antagonists & inhibitors
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Viral Proteins / genetics
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Viral Proteins / metabolism*
Substances
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Amines
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Antiviral Agents
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Proton Pump Inhibitors
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Proton Pumps
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Silanes
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Viral Proteins