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Dissecting Plasmodium falciparum EXP1/GST2 for xenobiotic defence in glucose-6-phosphate dehydrogenase deficiency

Grant number: 16/24790-9
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): May 01, 2017
Effective date (End): July 31, 2018
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Carsten Wrenger
Grantee:Kamila Anna Meissner
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Malaria is one of the most dangerous tropical diseases of our time with more than one million deaths per annum. The worst form of malaria, the malaria tropica, is caused by the parasite Plasmodium falciparum. However some genetic mutations or enzymopathies like glucose-6-phosphate dehydrogenase (G6PDH) deficiency are leading to a protection against severe falciparum malaria. Additionally G6PDH deficiency is causing a severe issue during drug discovery against malaria due to enhanced oxidative stress. Increased oxidative stress levels are harming cells by creating xenobiotics from cellular molecules. The detoxification of xenobiotics as well as applied drugs are carried out e.g. by coupling glutathione (GSH) to the respective molecules. Recently a novel type of glutathione S-transferases PfEXP1/GST2 has been discovered which is considered to be one potential target of the frontline malaria drug artemisinin. The proposed project intents to shed light on the plasmodial protein EXP1/GST2 in xenobiotic detoxification and G6PDH deficiency. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LUNEV, SERGEY; BUTZLOFF, SABINE; ROMERO, ATILIO R.; LINZKE, MARLEEN; BATISTA, FERNANDO A.; MEISSNER, KAMILA A.; MUELLER, INGRID B.; ADAWY, ALAA; WRENGER, CARSTEN; GROVES, MATTHEW R.. Oligomeric interfaces as a tool in drug discovery: Specific interference with activity of malate dehydrogenase of Plasmodium falciparum in vitro. PLoS One, v. 13, n. 4, . (12/12807-3, 14/23330-9, 13/10288-1, 16/24790-9, 15/26722-8)
VASCONCELOS, STANLEY N. S.; MEISSNER, KAMILA A.; FERRAZ, WITOR R.; TROSSINI, GUSTAVO H. G.; WRENGER, CARSTEN; STEFANI, HELIO A.. Indole-3-glyoxyl tyrosine: synthesis and antimalarial activity against Plasmodium falciparum. Future Medicinal Chemistry, v. 11, n. 6, p. 525-538, . (13/17960-7, 12/12807-3, 15/26722-8, 12/00424-2, 17/25543-8, 16/24790-9)
BATISTA, FERNANDO A.; BOSCH, SORAYA S.; BUTZLOFF, SABINE; LUNEV, SERGEY; MEISSNER, KAMILA A.; LINZKE, MARLEEN; ROMERO, ATILIO R.; WANG, CHAO; MUELLER, INGRID B.; DOMLING, ALEXANDER S. S.; et al. Oligomeric protein interference validates druggability of aspartate interconversion in Plasmodium falciparum. MICROBIOLOGYOPEN, v. 8, n. 7, . (17/03966-4, 15/26722-8, 16/24790-9, 14/23330-9, 13/17577-9)
MEISSNER, KAMILA ANNA; KRONENBERGER, THALES; MALTAROLLO, VINICIUS GONCALVES; GOULART TROSSINI, GUSTAVO HENRIQUE; WRENGER, CARSTEN. Targeting the Plasmodium falciparum plasmepsin V by ligand-based virtual screening. CHEMICAL BIOLOGY & DRUG DESIGN, v. 93, n. 3, p. 300-312, . (14/03644-9, 16/24790-9, 17/03966-4, 15/26722-8)

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