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SAF2011-27642

Financiado

EXPLORANDO NUEVAS ESTRATEGIAS TERAPEUTICAS PARA EL TRATAMIENTO DE ENFERMEDADES I...

EXPLORANDO NUEVAS ESTRATEGIAS TERAPEUTICAS PARA EL TRATAMIENTO DE ENFERMEDADES INFECCIOSAS Y PARASITARIAS TUBERCULOSIS AND MALARIA ARE AMONGST THE MAJOR WORLDWIDE HEALTH THREATS. MOREOVER, THEIR IMPACT, ESPECIALLY IN UNDERDEVELOPED COUNTRIES, IS BECOMING MORE DEVASTATING DUE TO THE OCCURRENCE OF MULTIDRUG RESISTANT STRAINS, DRUG SIDE... ver más

01/01/2011

169K€

Presupuesto del proyecto: 169K€

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UNIVERSIDAD DE BARCELONA No se ha especificado una descripción o un objeto social para esta compañía.

Total investigadores 328

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Financiación concedida El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2011-01-01

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UNIVERSIDAD DE BARCELONA

Total investigadores 328

Presupuesto del proyecto 169K€

Descripción del proyecto TUBERCULOSIS AND MALARIA ARE AMONGST THE MAJOR WORLDWIDE HEALTH THREATS. MOREOVER, THEIR IMPACT, ESPECIALLY IN UNDERDEVELOPED COUNTRIES, IS BECOMING MORE DEVASTATING DUE TO THE OCCURRENCE OF MULTIDRUG RESISTANT STRAINS, DRUG SIDE EFFECTS, AND CO-INFECTIONS. ON THE OTHER HAND, CHAGAS DISEASE IS ONE OF THE MOST WIDESPREAD LETHAL DISEASES TRANSMITTED BY BLOODSUCKING INSECTS, LEADING TO A DEATH TOLL OF 15 000 PERSONS PER YEAR. THUS, A DEEPER KNOWLEDGE ABOUT THE UNDERLYING BIOCHEMICAL PROCESSES ASSOCIATED WITH THESE DISEASES IS WORTH TO DEVELOP ALTERNATIVE THERAPEUTIC STRATEGIES BASED ON INNOVATIVE TARGETS. IN THIS CONTEXT, THIS PROJECT PURSUES TO EXAMINE THREE SPECIFIC PROTEINS: TRUNCATED HEMOGLOBIN N FROM M. TUBERCULOSIS (MTHBN), NITROPHORIN 7 FROM R. PROLIXUS, AND FINALLY GLUCOSE-6-PHOSPHATE DEHYDROGENASE FROM P. FALCIPARUM.FOLLOWING OUR PREVIOUS STUDIES (SAF2008-05595), WE WANT TO EXAMINE HERE THE INTERACTION OF MTHBN WITH FERREDOXINS, WHICH ARE CAPABLE TO RESTORE THE FERROUS STATE IN IN VITRO ASSAYS. ACCORDINGLY, THERE MUST BE AN EFFECTIVE INTERACTION BETWEEN MTHBN AND FERREDOXIN, AND KNOWLEDGE OF THE STRUCTURAL FEATURES OF SUCH INTERACTION CAN PROVIDE VALUABLE GUIDELINES FOR THE DEVELOPMENT OF INHIBITORS THAT CAN IMPEDE THE PROTEIN-PROTEIN ASSOCIATION AND THUS INTERFERE WITH THE NO DIOXYGENASE ROLE PLAYED BY MTHBN.IN CONTRAST TO MTHBN, NITROPHORINS (NPS) SEEMS TO PLAY A ROLE AS NO CARRIER, AND RELEASE OF NO TO BLOOD FACILITATES FEEDING OF THE BLOODSUCKING INSECT, WHICH CAN THEN SPREAD THE PROTOZOAN T. CRUZI,. UNDERSTANDING THE IMPACT OF THE PECULIAR STRUCTURAL PROPERTIES FOUND IN NP7 ON THE LIGAND MIGRATION PROPERTIES IS USEFUL TO SHED LIGHT INTO THE MOLECULAR MECHANISM OF ACTION, AND PARTICULARLY ON THE ROLE OF DISTINCT NPS IN THE LIFE STAGES OF THE BLOODSUCKING INSECT.FINALLY, THE IDENTIFICATION OF A SINGLE, BUT CHEMICALLY SIGNIFICANT MUTATION IN THE SUBSTRATE BINDING SITE OF G6PD, TOGETHER WITH THE RECENTLY REPORTED ENHANCED REACTIVITY OF A LYS PRESENT IN THE ACTIVE SITE, OPENS NEW AVENUES FOR THE DEVELOPMENT OF NOVEL THERAPEUTIC DRUGS EFFECTIVE AGAINST MALARIA. UBERCULOSIS\GLUCOSA-6-FOSFATO DESHIDROGENASA\MALARIA\NITROFORINA-7\ENFERMEDAD DE CHAGAS\HEMOGLOBINA TRUNACADA N

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