252002-58-7Relevant academic research and scientific papers
Development, synthesis and structure–activity-relationships of inhibitors of the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and Burkholderia pseudomallei
Seufert, Florian,Kuhn, Maximilian,Hein, Michael,Weiwad, Matthias,Vivoli, Mirella,Norville, Isobel H.,Sarkar-Tyson, Mitali,Marshall, Laura E.,Schweimer, Kristian,Bruhn, Heike,R?sch, Paul,Harmer, Nicholas J.,Sotriffer, Christoph A.,Holzgrabe, Ulrike
, p. 5134 - 5147 (2016/10/24)
The bacteria Burkholderia pseudomallei and Legionella pneumophila cause severe diseases like melioidosis and Legionnaire's disease with high mortality rates despite antibiotic treatment. Due to increasing antibiotic resistances against these and other Gram-negative bacteria, alternative therapeutical strategies are in urgent demand. As a virulence factor, the macrophage infectivity potentiator (Mip) protein constitutes an attractive target. The Mip proteins of B. pseudomallei and L. pneumophila exhibit peptidyl-prolyl cis/trans isomerase (PPIase) activity and belong to the PPIase superfamily. In previous studies, the pipecolic acid moiety proved to be a valuable scaffold for inhibiting this PPIase activity. Thus, a library of pipecolic acid derivatives was established guided by structural information and computational analyses of the binding site and possible binding modes. Stability and toxicity considerations were taken into account in iterative extensions of the library. Synthesis and evaluation of the compounds in PPIase assays resulted in highly active inhibitors. The activities can be interpreted in terms of a common binding mode obtained by docking calculations.
Pipecolic acid derivatives as small-molecule inhibitors of the legionella MIP protein
Juli, Christina,Sippel, Martin,J?ger, Jens,Thiele, Alexandra,Weiwad, Matthias,Schweimer, Kristian,R?sch, Paul,Steinert, Michael,Sotriffer, Christoph A.,Holzgrabe, Ulrike
, p. 277 - 283 (2011/03/22)
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 a
