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

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journal contribution
posted on 13.01.2011, 00:00 by Christina Juli, Martin Sippel, Jens Jäger, Alexandra Thiele, Matthias Weiwad, Kristian Schweimer, Paul Rösch, Michael Steinert, Christoph A. Sotriffer, Ulrike Holzgrabe
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.