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| Author(s): |
Raquel Maria Simão Gurge
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2017-07-04 |
| Examining board members: |
Alejandro Miguel Katzin;
Cristina Northfleet de Albuquerque;
José Franco da Silveira Filho;
Anita Hilda Straus Takahashi;
Erika Suzuki de Toledo
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| Advisor: | Alejandro Miguel Katzin; Gerhard Wunderlich |
| Abstract | |
The development of antimalarials is necessary because there are Plasmodium strains resistant to the drugs in use and an important target is the isoprenoid pathway. Targets derived from the isoprenoid pathway are: heme O as there are antimalarial drugs related to heme; And gibberillin, because there are inhibitors which are not harmful to man. Inabenfide (INA) and uniconazole-P (UNP) inhibit biosynthesis of gibberillin in plants and of growth the P. falciparum. Initially, we identified in P. falciparum genes homologous to cox10 and 15 encoding the enzymes (HOS and HAS) for synthesis of heme O and A. We created transgenic parasite lines which had HOS and HAS tagged to GFP. These revealed that the subcellular location of cox10 is in the nucleus and of cox15 in mitochondria. We identified heme O by metabolic labeling and mass spectrometry. However, no heme A or gibberellin was detected. INA and UNP decreased heme O biosynthesis and parasitemia as observed by oxido-reduction and metabolic labeling. Our data point to heme O as an important target for antimalarials. (AU) | |
| FAPESP's process: | 12/20273-9 - Characterization of the heme O, the heme A and enzymes homologous to COX10 and COX15 during intra-erythrocytic development of Plasmodium falciparum. |
| Grantee: | Raquel Maria Simão Gurge |
| Support Opportunities: | Scholarships in Brazil - Doctorate |