Interactómica, análisis estructural y búsqueda de fármacos: Aplicaciones a sistemas proteolíticos y a modelos amiloidogénicos

In this research project we intend to develop previous experimental and computational proteomics tools to identify interactions and relationships among proteins and ligands, as well as characterizing those molecules in depth, bringing some of them to the initial applicative stages of drug design/discovery. Efforts will be made to apply those approaches, in the chemogenomics and molecular imaging context, to crude and complex bilogical samples and/or to in vivo models. To develop these applications we shall aminly select proteolytic systems -proteases and inhibitors-, predominantly related with metallocarboxypeptidases in wich our groups have a good experience, as well as amyloidogenic models, with biotechnological and biomedical potentialities in both cases. In certain systems, like the ones related with Plasmodium and trypanosome species responsible for malaria and Chagas diseases, respectively, we shall first undertake a deep structural- functional characterization of the selected molecules. Later on, we shall develop a detailed program of ligand and drug design. In others, we shall use the previous background, generated by different groups, including ours, to develop a drug design program in a more inmediate way, like in subjects related with fibrinolytic and amyloidogenic disorders. In parallel, highthroughput and affinity screening procedures will be used to search for new molecules as lead compounds in extracts from selected living organisms (i.e. flora and fauna from central and south America), as a complement to the above mentioned drug discovery effort.