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Exploitation of key enzymes in the isoprenoid biosynthetic pathway as drug targets in leishmania

Objective

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 Scheme

CSC - Cost-sharing contracts

Coordinator

CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Address
Calle Ventanilla 11
18001 Granada
Spain

Participants (3)

FEDERAL UNIVERSITY OF RIO DE JANEIRO
Brazil
Address
S/n,edificio Do Centro De Ciencias Da Saude, Bloco G
21949-900 Rio De Janeiro
INSTITUTO VENEZOLANO DE INVESTIGACIONES CIENTIFICAS
Venezuela
Address
Km 11,Altos De Pipe, Km. 11, Carretera Panamericana
1020 Caracas
UNIVERSITY OF WALES CARDIFF
United Kingdom
Address
King Edward Vii Avenue, Redwood Building
CF10 3XF Cardiff