Figure 9.

General ABPP experiments for deconvolution of the mechanisms of artemisinin. A. Artemisinin‐alkyne probes are incubated with parasite‐infected cultures or other relevant Plasmodium proteomes. Iron‐mediated activation of the endoperoxide bridge generates radicals, which have been shown to be mostly secondary radicals. Extensive protein alkylation affects multiple essential pathways, overwhelms the parasite's protein repair systems, and leads to parasite death. B) Alkylated proteins were enriched with streptavidin after appending biotin to the probe‐protein complexes by click chemistry. Trypsinization of enriched proteins, followed by LC‐MS/MS analysis identified the alkylated proteins, which participate in essential parasite functions like antioxidant defense, the glycolytic pathway, DNA and protein synthesis, among others.