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-Doctoral
• Start date: May 01, 2017
• End date: July 31, 2018
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Agreement: 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

Abstract

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)

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)

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, MAR 2019. (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, JUL 2019. (17/03966-4, 15/26722-8, 16/24790-9, 14/23330-9, 13/17577-9)

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, APR 25 2018. (12/12807-3, 14/23330-9, 13/10288-1, 16/24790-9, 15/26722-8)

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, MAR 2019. (14/03644-9, 16/24790-9, 17/03966-4, 15/26722-8)