ArticleProceedings of the National Academy of Sciences of the United States of America2011
Bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 142 citations in OpenAlex.
- Synthesis and Evaluation of Peptoid-Based Compound Libraries as Inhibitors of Parasite Metallo-Aminopeptidases.ChemMedChem · 2026Article
- Hydroxamate-based inhibitors reveal structural determinants of selectivity for Plasmodium falciparum aminopeptidase P.The Journal of biological chemistry · 2026Article
- Natural triterpenic phenolic esters target PfA-M17 in Plasmodium falciparum.Malaria journal · 2026Article
- Guidelines for the Design of Custom Affinity-Based Probes for Metalloproteases.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Chemoproteomics validates selective targeting ofeLife · 2024Article
- Identification and Validation of Compounds TargetingACS infectious diseases · 2024Article
- Article
- The Digestive Vacuole of the Malaria Parasite: A Specialized Lysosome.Pathogens (Basel, Switzerland) · 2024Review
- Identification of a potent and selective LAPTc inhibitor by RapidFire-Mass Spectrometry, with antichagasic activity.PLoS neglected tropical diseases · 2024Article
- Ubenimex combined with Albendazole for the treatment ofFrontiers in veterinary science · 2024Article
- Recent Progress of Activity-Based Fluorescent Probes for Imaging Leucine Aminopeptidase.Biosensors · 2023Review
- Marine Invertebrates: A Promissory Still Unexplored Source of Inhibitors of Biomedically Relevant Metallo Aminopeptidases Belonging to the M1 and M17 Families.Marine drugs · 2023Review
- Genetic and chemical validation ofeLife · 2022Article
- Review
- A metal ion-dependent conformational switch modulates activity of the Plasmodium M17 aminopeptidase.The Journal of biological chemistry · 2022Article
- Overexpression ofPathogens (Basel, Switzerland) · 2021Article
- Using microbial metalo-aminopeptidases as targets in human infectious diseases.Microbial cell (Graz, Austria) · 2021Review
- KBE009: A Bestatin-Like Inhibitor of theLife (Basel, Switzerland) · 2021Article
- Chemoproteomics for Plasmodium Parasite Drug Target Discovery.Chembiochem : a European journal of chemical biology · 2021Review
- Mapping the substrate specificity of the Plasmodium M1 and M17 aminopeptidases.The Biochemical journal · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Malaria causes worldwide morbidity and mortality, and while chemotherapy remains an excellent means of malaria control, drug-resistant parasites necessitate the discovery of new antimalarials. Peptidases are a promising class of drug targets and perform several important roles during the Plasmodium falciparum erythrocytic life cycle. Herein, we report a multidisciplinary effort combining activity-based protein profiling, biochemical, and peptidomic approaches to functionally analyze two genetically essential P. falciparum metallo-aminopeptidases (MAPs), PfA-M1 and Pf-LAP. Through the synthesis of a suite of activity-based probes (ABPs) based on the general MAP inhibitor scaffold, bestatin, we generated specific ABPs for these two enzymes. Specific inhibition of PfA-M1 caused swelling of the parasite digestive vacuole and prevented proteolysis of hemoglobin (Hb)-derived oligopeptides, likely starving the parasite resulting in death. In contrast, inhibition of Pf-LAP was lethal to parasites early in the life cycle, prior to the onset of Hb degradation suggesting that Pf-LAP has an essential role outside of Hb digestion.
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Registered trials
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