Pipecolic acid derivatives as small-molecule inhibitors of the Legionella MIP protein.
Juli C, Sippel M, Jäger J, Thiele A, Weiwad M, Schweimer K, Rösch P, Steinert M, Sotriffer CA, Holzgrabe U.
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.