Abstract
Seventy-two hundred potential inhibitors of the histone deacetylase (HDAC) enzyme family, based on a 1,3-dioxane diversity structure, were synthesized on polystyrene macrobeads. The compounds were arrayed for biological assays in a "one bead-one stock solution" format. Metal-chelating functional groups were used to direct the 1,3-dioxanes to HDAC enzymes, which are zinc hydrolases. Representative structures from this library were tested for inhibitory activity and the 1,3-dioxane structure was shown to be compatible with HDAC inhibition. [structure: see text]
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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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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Histone Deacetylase Inhibitors*
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Histone Deacetylases / chemistry
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Hydroxamic Acids / chemical synthesis*
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Hydroxamic Acids / chemistry
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Hydroxamic Acids / pharmacology
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Peptides*
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Sequence Homology, Amino Acid
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Peptides
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trapoxin A
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Histone Deacetylases