en
Doctoral thesis
Open access
English

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

Defense date2013-02-11
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.

eng
Keywords
  • Plasmodium falciparum
  • Malaria
  • Target identification
  • Chemical proteomics
  • Inverse screening
  • PfCDPK2
  • PfH45
  • PfHsp90
  • PfMDR2
  • Protein expression and purification
  • Protein crystallization
  • Biochemical characterization
Citation (ISO format)
LAUCIELLO, Leonardo. From compound to target: chemical proteomics and in silico screening for target identification in Plasmodium falciparum. 2013. doi: 10.13097/archive-ouverte/unige:30027
Main files (1)
Thesis
accessLevelPublic
Identifiers
1225views
311downloads

Technical informations

Creation09/27/2013 10:44:00 AM
First validation09/27/2013 10:44:00 AM
Update time03/14/2023 8:31:22 PM
Status update03/14/2023 8:31:22 PM
Last indexation01/29/2024 7:56:19 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack