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© Artur Scherf
Scanning Electron Microscopy of Red Blood Cell infected by Plasmodium falciparum.
Publication : ACS infectious diseases

Development of a Photo-Cross-Linkable Diaminoquinazoline Inhibitor for Target Identification in Plasmodium falciparum

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in ACS infectious diseases - 05 Feb 2018

Lubin AS, Rueda-Zubiaurre A, Matthews H, Baumann H, Fisher FR, Morales-Sanfrutos J, Hadavizadeh KS, Nardella F, Tate EW, Baum J, Scherf A, Fuchter MJ

Link to Pubmed [PMID] – 29377668

ACS Infect Dis 2018 04;4(4):523-530

Diaminoquinazolines represent a privileged scaffold for antimalarial discovery, including use as putative Plasmodium histone lysine methyltransferase inhibitors. Despite this, robust evidence for their molecular targets is lacking. Here we report the design and development of a small-molecule photo-cross-linkable probe to investigate the targets of our diaminoquinazoline series. We demonstrate the effectiveness of our designed probe for photoaffinity labeling of Plasmodium lysates and identify similarities between the target profiles of the probe and the representative diaminoquinazoline BIX-01294. Initial pull-down proteomics experiments identified 104 proteins from different classes, many of which are essential, highlighting the suitability of the developed probe as a valuable tool for target identification in Plasmodium falciparum.

https://www.ncbi.nlm.nih.gov/pubmed/29377668