Obiettivo Both dihydrofolate reductase-thymidylate synthase (DHR-TS) and DHFR from P. vivax will be cloned and expressed from E.coli. The kinetic properties of the expressed enzyme and the profiles of inhibition by various antifolates will be studied, in order to find out whether it is inherently resistant to inhibition. Mutants of P.vivax DHFR, both found in the field and artificially designed, as well as mutants of P.falciparum will be made and studied. The results will be used to model the three-dimensional structure of the enzymes, especially around the active site. Both DHFR and DHFR-TS from the two sources will be prepared in sufficient amounts for crystallization and structure determination by X-ray diffraction. Newly designed antifolates and those synthesized previously will be tested for their inhibitory activities. The mode of binding of such agents to the enzyme will be studied both from modelling and X-ray studies. Such agents will be important as leads to new antifolate drugs against both types of malaria. Agents with activity against both P. vivax and P.falciparum DHFR will be of special interest, in view of the common occurrence of mixed infections. Campo scientifico medical and health scienceshealth sciencesinfectious diseasesmalarianatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programma(i) FP5-INCO 2 - Programme for research, technological development and demonstration on "Confirming the international role of Community research,1998-2002" Argomento(i) Data not available Invito a presentare proposte Data not available Meccanismo di finanziamento CSC - Cost-sharing contracts Coordinatore THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Contributo UE Nessun dato Indirizzo South Parks Road OX1 3QY OXFORD Regno Unito Mostra sulla mappa Costo totale Nessun dato Partecipanti (3) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY India Contributo UE Nessun dato Indirizzo Aruna Asaf Ali marg 10504 NEW DELHI Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato THAILAND NATIONAL SCIENCE AND TECHNOLOGY DEVELOPMENT AGENCY Thailandia Contributo UE Nessun dato Indirizzo Rama 6 Road 73-1 10400 BANGKOK Mostra sulla mappa Costo totale Nessun dato UNIVERSITY OF MODENA AND REGGIO EMILIA Italia Contributo UE Nessun dato Indirizzo Via Campi 183 41100 MODENA Mostra sulla mappa Costo totale Nessun dato