Targeting the Plasmodium falciparum IspE Enzyme
Year: 2024
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide The enzyme IspE in Plasmodium falciparum is considered an attractive drug target, as it is essential for parasite survival and is absent in the human proteome. Yet it still has not been addressed by a small-molecule inhibitor. In this study, we conducted a high-throughput screening campaign against the Pf IspE enzyme. Our approach toward a Pf IspE inhibitor comprises in vitro screening, structure–activity relationship studies, examining the docking position using an AlphaFold model, and finally target verification through probe binding and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The newly synthesized probe containing a diazirine and an alkyne moiety ( 23 ) allowed us to demonstrate its binding to IspE in the presence of a lysate of human cells (HEK293 cells) and to get evidence that both probe 23 and the best inhibitor of the series ( 19 ) compete for the same IspE binding site.
Source: ACS Omega
Authors: Eleonora Diamanti, Annina M. Steinbach, Lais P. de Carvalho, Henni-Karoliina Ropponen, Antoine Lacour, Rawia Hamid, Sidra Eisa, Patricia Bravo, Spyridon Bousis, Boris Illarionov, Markus Fischer, Mostafa M. Hamed, Nina C. Bach, Matthias Rottmann, Jana Held, Matthias Witschel, Stephan A. Sieber, Anna K. H. Hirsch
Institutions: Helmholtz Centre for Infection Research, Helmholtz Institute for Pharmaceutical Research Saarland, Saarland University, Technical University of Munich, University of Tübingen, Swiss Tropical and Public Health Institute, University of Basel, Universität Hamburg, German Center for Infection Research, BASF (Germany)
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,935
Award: G5789606266
OpenAlex ID: W4403759194