Use of a Photo-crosslinkable Diaminoquinazoline Inhibitor for Target Identification in Plasmodium Falciparum

Diaminoquinazolines represent a privileged scaffold for antimalarial discovery, including use as putative Plasmodium histone lysine methyltransferase inhibitors (BIX-01294). Despite this, robust evidence for their molecular targets, proteome-wide, is lacking. Here we report the design and development of a small-molecule photo-crosslinkable probe to investigate the targets of our diaminoquinazoline series. We demonstrate the effectiveness of our designed probe for photoaffinity labelling of Plasmodium lysates and initial pull-down proteomics experiments identified proteins from different classes enriched by the probe, highlighting the suitability of the developed probe as a valuable tool for protein identification in Plasmodium falciparum.