Abstract
Pilicides block pili formation by binding to pilus chaperones and blocking their function in the chaperone/usher pathway in E. coli. Various C-2 substituents were introduced on the pilicide scaffold by design and synthetic method developments. Experimental evaluation showed that proper substitution of this position affected the biological activity of the compound. Aryl substituents resulted in pilicides with significantly increased potencies as measured in pili-dependent biofilm and hemagglutination assays. The structural basis of the PapD chaperone-pilicide interactions was determined by X-ray crystallography.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Binding Sites
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Biofilms / drug effects
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Crystallography, X-Ray
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Escherichia coli / drug effects*
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Escherichia coli / pathogenicity
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Escherichia coli / physiology
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Escherichia coli Proteins / chemistry
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Fimbriae, Bacterial / drug effects*
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Hemagglutination Tests
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Hydrophobic and Hydrophilic Interactions
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Models, Molecular
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Molecular Chaperones / chemistry
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Molecular Structure
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Periplasmic Proteins / chemistry
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Protein Subunits / chemistry
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Pyridones / chemical synthesis*
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Pyridones / chemistry
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Pyridones / pharmacology
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / chemistry
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Thiazoles / pharmacology
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Virulence / drug effects
Substances
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Anti-Bacterial Agents
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Escherichia coli Proteins
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Molecular Chaperones
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PapD protein, E coli
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Periplasmic Proteins
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Protein Subunits
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Pyridones
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Thiazoles