2023
DOI: 10.1101/2023.07.03.547579
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Covalent macrocyclic proteasome inhibitors mitigate resistance inPlasmodium falciparum

John M. Bennett,
Kurt E. Ward,
Ryan Muir
et al.

Abstract: The Plasmodium proteasome is a promising antimalarial drug target due to its essential role in all parasite lifecycle stages. Furthermore, proteasome inhibitors have synergistic effects when combined with current first-line artemisinins. Linear peptides that covalently inhibit the proteasome are effective at killing parasites and have a low propensity for inducing resistance. However, these scaffolds generally suffer from poor pharmacokinetics and bioavailability. Here we describe the development of covalent, … Show more

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