The Plasmodium falciparum proteasome as a drug target

摘要: Abstract The proteasome is a highly efficient multi-subunit enzyme complex which degrades cellular proteins that have been labeled with ubiquitin molecules. has core contains three types of catalytic subunit β1, β2, and β5, substrate preferences are similar to caspase, trypsin, chymotrypsin, respectively. Proteasome inhibitors already developed act against the human as potential anticancer agents. Research now investigating antimalarial agents acting selectively on parasite’s proteasome, rather than proteasomes. Irreversible reversible both considered. contain functional group such lactone, epoxyketone, vinyl sulfone, or sulfonyl fluoride capable reacting N-terminal threonine residue subunits form covalent adduct. Reversible include asparagine ethylenediamines, aldehydes, peptide boronates, cyclic peptides. It demonstrated selectivity for Plasmodium feasible by taking advantage structural differences between binding pockets relevant subunits. Differences sensitivity parasite proteasomes selective inhibition specific also offer opportunities design inhibitors. Inhibitors inhibiting β2 β5 but only predicted be potent minimal host cell toxicity.