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Proteins, Expression, Isolation and Analysis | MATERIALS AND METHODS Materials Artemisinin (QHS), dihydroartemisinin (DHA), 2,2′-bipyridyl (BiPy), deferiprone (DFP), E64d, ALLN and glucosamine (GlcN) were purchased from Sigma-Aldrich; Syto-61 and calcein-AM were from Life Technologies; streptavidin–agarose was from GenScript; protease inhibitor cocktail was from Roche; streptavidin–horseradish-peroxidase (HRP) conjugate and the BCA Protein Assay Kit were from Pierce. | Get A Quote |
Current first-line artemisinin antimalarials are threatened by the emergence of resistant Plasmodium falciparum. Decreased sensitivity is evident in the initial (early ring) stage of intraerythrocytic development, meaning that it is crucial to understand the action of artemisinins at this stage. Here, we examined the roles of iron (Fe) ions and haem in artemisinin activation in early rings using Fe ion chelators and a specific haemoglobinase inhibitor (E64d). Quantitative modelling of the antagonism accounted for its complex dependence on the chemical features of the artemisinins and on the drug exposure time, and showed that almost all artemisinin activity in early rings (>80%) is due to haem-mediated activati... More