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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wong, Michael H. L. Biagini, Giancarlo A. Barton, Victoria Charoensutthivarakul, Sitthivut Ward, Stephen A. Phanchana, Matthew O'neill, Paul M. Ismail, Hanafy M. Hemingway, Janet |
| Description | Author Affiliation: Ismail HM ( Research Centre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom); Barton V ( Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, United Kingdom.); Phanchana M ( Research Centre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom); Charoensutthivarakul S ( Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, United Kingdom.); Wong MH ( Vector Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom); Hemingway J ( Vector Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom); Biagini GA ( Research Centre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom); O'Neill PM ( Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, United Kingdom.); Ward SA ( Research Centre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom); |
| Abstract | The artemisinin (ART)-based antimalarials have contributed significantly to reducing global malaria deaths over the past decade, but we still do not know how they kill parasites. To gain greater insight into the potential mechanisms of ART drug action, we developed a suite of ART activity-based protein profiling probes to identify parasite protein drug targets in situ. Probes were designed to retain biological activity and alkylate the molecular target(s) of Plasmodium falciparum 3D7 parasites in situ. Proteins tagged with the ART probe can then be isolated using click chemistry before identification by liquid chromatography-MS/MS. Using these probes, we define an ART proteome that shows alkylated targets in the glycolytic, hemoglobin degradation, antioxidant defense, and protein synthesis pathways, processes essential for parasite survival. This work reveals the pleiotropic nature of the biological functions targeted by this important class of antimalarial drugs. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 113 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2016-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antimalarials Artemisinins Lactones Life Cycle Stages Drug Effects Molecular Probes Plasmodium Falciparum Metabolism Protozoan Proteins Chemical Synthesis Chemistry Pharmacology Click Chemistry Antagonists & Inhibitors Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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