Substrate Peptidomimetic Inhibitors of P. falciparum Plasmepsin X with Potent Antimalarial Activity.

ABSTRACT: Plasmepsin X (PMX) is an aspartyl protease that processes proteins essential for Plasmodium parasites to invade and egress from host erythrocytes during the symptomatic asexual stage of malaria. PMX substrates possess a conserved cleavage region denoted by the consensus motif, SFhE (h=hydrophobic amino acid). Peptidomimetics reflecting the P₃ -P₁ positions of the consensus motif were designed and showed potent and selective inhibition of PMX. It was established that PMX prefers Phe in the P₁ position, di-substitution at the β-carbon of the P₂ moiety and a hydrophobic P₃ group which was supported by modelling of the peptidomimetics in complex with PMX. The peptidomimetics were shown to arrest asexual P. falciparum parasites at the schiz

SUBMITTER: Richardson LW 

PROVIDER: S-EPMC9804387 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature