Abstract
A series of C3 O-functionalized 2-acetamido-2-deoxy-Δ⁴-β-D-glucuronides were synthesized to explore noncharge interactions in subsite 2 of the influenza virus sialidase active site. In complex with A/N8 sialidase, the parent compound (C3 OH) inverts its solution conformation to bind with all substituents well positioned in the active site. The parent compound inhibits influenza virus sialidase at a sub-μM level; the introduction of small alkyl substituents or an acetyl group at C3 is also tolerated.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetamides / chemical synthesis
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Acetamides / chemistry*
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Antiviral Agents / chemistry*
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Catalytic Domain
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Enzyme Assays
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Fluorometry
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Glucuronides / chemical synthesis
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Glucuronides / chemistry*
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Hydrophobic and Hydrophilic Interactions
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Models, Molecular
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Neuraminidase / antagonists & inhibitors
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Neuraminidase / chemistry*
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Orthomyxoviridae / enzymology*
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Static Electricity
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Structure-Activity Relationship
Substances
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Acetamides
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Antiviral Agents
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Glucuronides
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Neuraminidase