Abstract
The macrophage infectivity potentiator (MIP) protein is a major virulence factor of Legionella pneumophila, the causative agent of Legionnaires' disease. MIP belongs to the FK506-binding proteins (FKBP) and is necessary for optimal intracellular survival and lung tissue dissemination of L. pneumophila. We aimed to identify new small-molecule inhibitors of MIP by starting from known FKBP12 ligands. Computational analysis, synthesis, and biological testing of pipecolic acid derivatives revealed a promising scaffold for new MIP inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bacterial Proteins / antagonists & inhibitors*
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Bacterial Proteins / chemistry
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Binding Sites
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Cell Line
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Colony Count, Microbial
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Guinea Pigs
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Legionella pneumophila / drug effects*
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Legionella pneumophila / enzymology
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Legionnaires' Disease / drug therapy
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Peptidylprolyl Isomerase / antagonists & inhibitors*
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Peptidylprolyl Isomerase / chemistry
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Pipecolic Acids / chemical synthesis*
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Pipecolic Acids / chemistry
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Pipecolic Acids / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
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Tacrolimus Binding Protein 1A / chemistry
Substances
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Bacterial Proteins
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Pipecolic Acids
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Tacrolimus Binding Protein 1A
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Mip protein, Legionella pneumophila
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Peptidylprolyl Isomerase