High Affinity Inhibitors of the Macrophage Infectivity Potentiator Protein from <i>Trypanosoma cruzi</i>, <i>Burkholderia pseudomallei</i>, and <i>Legionella pneumophila</i>─A Comparison.

ABSTRACT: Since Chagas disease, melioidosis, and Legionnaires' disease are all potentially life-threatening infections, there is an urgent need for new treatment strategies. All causative agents, Trypanosoma cruzi, Burkholderia pseudomallei, and Legionella pneumophila, express a virulence factor, the macrophage infectivity potentiator (MIP) protein, emerging as a promising new therapeutic target. Inhibition of MIP proteins having a peptidyl-prolyl isomerase activity leads to reduced viability, proliferation, and cell invasion. The affinity of a series of pipecolic acid-type MIP inhibitors was evaluated against all MIPs using a fluorescence polarization assay. The analysis of structure-activity relationships led to highly active inhibitors of MIPs of all pathogens, characterized

SUBMITTER: Lohr T 

PROVIDER: S-EPMC11476723 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature