title: Pipecolic acid derivatives as small-molecule inhibitors of the Legionella MIP protein.
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.
authors.affiliation: Institute of Pharmacy and Food Chemistry, University of Würzburg, Würzburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Juli
authors.forename: Martin
authors.initials: M
authors.lastname: Sippel
authors.forename: Jens
authors.initials: J
authors.lastname: Jäger
authors.forename: Alexandra
authors.initials: A
authors.lastname: Thiele
authors.forename: Matthias
authors.initials: M
authors.lastname: Weiwad
authors.forename: Kristian
authors.initials: K
authors.lastname: Schweimer
authors.forename: Paul
authors.initials: P
authors.lastname: Rösch
authors.forename: Michael
authors.initials: M
authors.lastname: Steinert
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Sotriffer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001665:Binding Sites; D002460:Cell Line; D015169:Colony Count, Microbial; D006168:Guinea Pigs; D016952:Legionella pneumophila / Q000187:drug effects* / Q000201:enzymology; D007877:Legionnaires' Disease / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010875:Pipecolic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D022061:Tacrolimus Binding Protein 1A / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D010875:Pipecolic Acids; D022061:Tacrolimus Binding Protein 1A; C512922:Mip protein, Legionella pneumophila; D019696:Peptidylprolyl Isomerase