Structure-based design of novel aminopeptidase inhibitors
PfMAP Inhibitors. Malaria remains a global health issue. Up to 48% of the world’s population (3 billion people), now live in areas at risk of malaria. The malaria parasite Plasmodium falciparum's metalloaminopeptidases (PfMAPs), M1, M17 and M18 are essential for parasite fitness. Agents that inhibit the PfMAPs in combination is desirable as this would reduce the likelihood of parasites being able to rapidly evolve resistance. In this project, biochemistry and protein crystallography will be used to identify how molecules are trafficked to the buried active sites of multimeric PfMAPs and SAR-guided and structure-based drug design approaches will be applied to the development of novel dual and tripeptidase inhibitors.