Targeting the Plasmodium falciparum IspE Enzyme.

ABSTRACT: 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 PfIspE enzyme. Our approach toward a PfIspE 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

SUBMITTER: Diamanti E 

PROVIDER: S-EPMC11541488 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature