The proposal describes how steps will be made to advance in the knowledge of is oprenoid biosynthesis in order to produce specific inhibitors that will be of use in the treatment of the leishamniases. Focus will be placed on the development of inhbitors against two enzymes: farnesyl diphosphate syntheses and squalling syntheses. Advantage will be taken of the existing knowledge on the inhibition of these enzymes in other organisms and of the crystal structures available for the modelling of the active site of the protozoan enzymes and identification of lead molecules. Alterations in is oprenoid composition, effects on parasite ultrustructural morphology and the intracellular localization of these enzymes will be studied in order to use the information in understanding drug toxicity, mode of action and intracellular transport requirements.
Funding SchemeCSC - Cost-sharing contracts
21949-900 Rio De Janeiro
CF10 3XF Cardiff