Abstract
The first phosphonate inhibitors of antigen 85C--a major protein component of the Mycobacterium tuberculosis cell wall possessing mycolyltransferase activity were prepared using structure-based design. These potential novel antituberculosis agents, consisting of a phosphonate moiety, hydrophobic alkyl chain and a simple trehalose-mimicking aromatic structure, were designed as tetrahedral transition-state analogue inhibitors of antigen 85C, which catalyzes the key mycolyltransferase reaction involved in cell wall biosynthesis.
MeSH terms
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Acyltransferases / antagonists & inhibitors*
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Acyltransferases / chemistry
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Acyltransferases / metabolism
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Antigens, Bacterial / metabolism
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Antitubercular Agents / chemistry*
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Antitubercular Agents / pharmacology
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Binding Sites
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Catalysis
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Cell Wall / chemistry
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Cell Wall / drug effects
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Cell Wall / metabolism*
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Hydrocarbons, Aromatic / chemistry
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Hydrophobic and Hydrophilic Interactions
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Inhibitory Concentration 50
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Models, Chemical
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Molecular Mimicry
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Mycobacterium tuberculosis / enzymology
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Mycobacterium tuberculosis / metabolism*
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Organophosphonates / chemistry
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Organophosphonates / pharmacology*
Substances
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Antigens, Bacterial
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Antitubercular Agents
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Hydrocarbons, Aromatic
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Organophosphonates
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Acyltransferases
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antigen 85C, Mycobacterium tuberculosis
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trehalose mycolyltransferase