Abstract
Fluoroneplanocin A (12) was designed as a novel mechanism-based inhibitor of S-adenosylhomocysteine hydrolase (SAH) and efficiently synthesized via an electrophilic vinyl fluorination reaction (n-BuLi, N-fluorobenzenesulfonimide at -78 degrees C). Fluoroneplanocin A exhibited 2-fold more potent SAH inhibitory activity than the parent neplanocin A. A new mechanism of irreversible inhibition discovered in this work might provide new alternatives in the design of a different class of antiviral agents operating via SAH inhibition.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine / analogs & derivatives
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Adenosine / chemical synthesis*
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Adenosine / chemistry
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Adenosine / pharmacology
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Adenosylhomocysteinase
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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 / pharmacology
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Cell Line
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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HIV-1 / drug effects
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Herpesvirus 1, Human / drug effects
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Herpesvirus 2, Human / drug effects
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Humans
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Hydrolases / antagonists & inhibitors*
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Vesicular stomatitis Indiana virus / drug effects
Substances
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Antiviral Agents
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Enzyme Inhibitors
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fluoroneplanocin A
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Hydrolases
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Adenosylhomocysteinase
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Adenosine