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From compound to target: chemical proteomics and in silico screening for target identification in Plasmodium falciparum

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Defense Thèse de doctorat : Univ. Genève, 2013 - Sc. 4531 - 2013/02/11
Abstract Malaria is a parasitic disease caused by protozoan parasites of the genus Plasmodium. The World Health Organisation (WHO) estimates that out of the more than 650000 people who died in 2010, 86% were children under the age of 5. New drugs and drug targets are thus needed to guarantee the future of antimalarial therapies. Affinity chromatography (chapter 2) and in silico screening methods (chapter 3) have been used to identify the potential target(s) of an azabicyclo[3.2.2]nonane (compound 1) and triclosan (TCL). The proposed targets of compound 1 (RNA helicase-1 and Heat-shock protein 90) and of TCL (multidrug resistance protein 2 and calcium-dependent protein kinase 2) were recombinantly expressed and the activity of compounds was verified. This study allowed the first steps towards the confirmation of putative targets of two prospective antimalarials, and it led to the development of new methods needed to further characterize the proposed target proteins.
Keywords Plasmodium falciparumMalariaTarget identificationChemical proteomicsInverse screeningPfCDPK2PfH45PfHsp90PfMDR2Protein expression and purificationProtein crystallizationBiochemical characterization
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URN: urn:nbn:ch:unige-300276
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LAUCIELLO, Leonardo. From compound to target: chemical proteomics and in silico screening for target identification in Plasmodium falciparum. Université de Genève. Thèse, 2013. https://archive-ouverte.unige.ch/unige:30027

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Deposited on : 2013-09-30

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