Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7

Ismail, Hanafy ORCID: https://orcid.org/0000-0002-9953-9588, Barton, Victoria, Phanchana, Matthew, Charoensutthivarakul, Sitthivut, Wong, Michael H L, Hemingway, Janet ORCID: https://orcid.org/0000-0002-3200-7173, Biagini, Giancarlo ORCID: https://orcid.org/0000-0001-6356-6595, O’Neill, Paul M and Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192 (2016) 'Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7'. Proceedings of the National Academy of Sciences, Vol 113, Issue 8, pp. 2080-2085.

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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.

Item Type:	Article
Subjects:	QX Parasitology > Protozoa > QX 135 Plasmodia QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1073/pnas.1600459113
Depositing User:	Carmel Bates
Date Deposited:	10 Mar 2016 13:40
Last Modified:	20 Oct 2017 08:28
URI:	https://archive.lstmed.ac.uk/id/eprint/5747

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