Structural dissection of nanoparticle-assisted drug delivery in human infectious d...
| Grant number: | 17/26358-0 |
| Support type: | Scholarships in Brazil - Doctorate |
| Effective date (Start): | May 01, 2018 |
| Effective date (End): | April 30, 2021 |
| Field of knowledge: | Biological Sciences - Parasitology |
| Principal Investigator: | Carsten Wrenger |
| Grantee: | Sun Liu Rei Yan |
| Home Institution: | Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated research grant: | 15/26722-8 - Drug discovery against human infectious diseases, AP.TEM |
Abstract The Malaria parasite Plasmodium falciparum possesses organelles such as mitochondrion and the chloroplast-like compartment named apicoplast which is absent in the human host. Interference with metabolic pathways present in the latter one has been proven be lethal for the parasite. This doctoral research project aims to identify antibacterial compounds by targeting the lipoic acid metabolism of S. aureus utilizing two different approaches: the lipoic acid salvage pathway will be addressed by suicide substrates mimicking natural substrates, resulting in generation of nonfunctional cofactors that poison all cofactor dependent enzymes. A second approach intends to identify enzyme inhibitors targeting lipoic acid biosynthesis enzymes. The results may not only validate enzymes of the lipoic acid biosynthesis and salvage pathway as attractive targets for novel therapeutic approaches, but also provide bioactive molecules for further drug development. The discovery of drugs interfering with the lipoic acid metabolism in Malaria possesses a novel drug target which is restricted to the parasite. (AU) | |