Pipecolic acid derivatives as small-molecule inhibitors of the Legionella MIP protein

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Juli, Christina ; Sippel, Martin ; Jäger, Jens ; Thiele, Alexandra ; Weiwad, Matthias ; Schweimer, Kristian ; Rösch, Paul ; Steinert, Michael ; Sotriffer, Christoph ; Holzgrabe, Ulrike:
Pipecolic acid derivatives as small-molecule inhibitors of the Legionella MIP protein.
In: Journal of Medicinal Chemistry. Bd. 54 (2011) Heft 1 . - S. 277-283.
ISSN 1520-4804
DOI: https://doi.org/10.1021/jm101156y

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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.