2 research outputs found
Identification of Potent and Selective Non-covalent Inhibitors of the Plasmodium falciparum Proteasome
We
have identified short N,C-capped peptides that selectively inhibit
the proteasome of the malaria-causing pathogen Plasmodium
falciparum. These compounds are highly potent in culture
with no toxicity in host cells. One cyclic biphenyl ether compound
inhibited intraerythrocytic growth of P. falciparum with an IC<sub>50</sub> of 35 nM, and we show that even a pulse
treatment with this cyclic peptide induced parasite death due to proteasome
inhibition. These compounds represent promising new antimalarial agents
that target the essential proteasomal machinery of the parasite without
toxicity toward the host
N,C-Capped Dipeptides with Selectivity for Mycobacterial Proteasome over Human Proteasomes: Role of S3 and S1 Binding Pockets
We identified N,C-capped
dipeptides that are selective for the Mycobacterium
tuberculosis proteasome over human
constitutive and immunoproteasomes. Differences in the S3 and S1 binding
pockets appeared to account for the species selectivity. The inhibitors
can penetrate mycobacteria and kill nonreplicating M. tuberculosis under nitrosative stress