Pipecolic Acid Derivatives As Small-Molecule Inhibitors of the Legionella MIP Protein

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• 作者：Christina Juli ; Martin Sippel ; Jens Ja虉ger ; Alexandra Thiele ; Matthias Weiwad ; Kristian Schweimer ; Paul Ro虉sch ; Michael Steinert ; Christoph A. Sotriffer ; Ulrike Holzgrabe
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：January 13, 2011
• 年：2011
• 卷：54
• 期：1
• 页码：277-283
• 全文大小：843K
• 年卷期：v.54,no.1(January 13, 2011)
• ISSN：1520-4804

文摘

The macrophage infectivity potentiator (MIP) protein is a major virulence factor of Legionella pneumophila, the causative agent of Legionnaires鈥?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.