Journal of medicinal and pharmaceutical chemistry 2011-01-13

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

Christina Juli, Martin Sippel, Jens Jäger, Alexandra Thiele, Matthias Weiwad, Kristian Schweimer, Paul Rösch, Michael Steinert, Christoph A Sotriffer, Ulrike Holzgrabe

Index: J. Med. Chem. 54 , 277-283, (2011)

Full Text: HTML

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.