Fragments derived from the structure of protease inhibitors with selectivity for inhibition of mammalian and microorganism enzymes and its role as an anti-inflammatory, antimicrobial, antithrombotic and anti- tumor agent: mechanism of action

Abstract

Brazilian flora is considered an important source of natural products that may be beneficial to all mankind. Studies of these resources require a concerted effort of the Brazilian scientific institutions. Our research group has been conducting comparative studies of protease inhibitors from leguminous seeds, determining the primary, secondary and tertiary structures, as well as modeling of proteins, in order to identify residues of specific amino acids involved in its interaction with the target protease. Characterization of the interactions between the natural protease inhibitors or technically modified proteases and their targets are being investigated in many biological processes such as inflammation, hemostasis and thrombosis, and tumor development. The research group has extensive experience in kinetic analysis of peptides used as substrates, enzyme inhibitors and agonists. This project proposes to continue the investigation using both proteins and synthetic peptides based on the structures of protease inhibitors and lectins, using models of inflammation, thrombosis and cancer, in vitro and in vivo, in an attempt to establish the involved mechanisms and the relationships between the structure and the kinetic parameters for inhibition of target proteases. Our purpose is to investigate possible therapeutic uses of these substances. The proposed project will provide conditions for continuation of the group's studies involved in the Thematic Project 2009/53766-5, coordinated by Prof. Dr. Maria Luiza V. Oliva, Department of Biochemistry UNIFESP- EPM that over several years have been evaluating the biological significance in the variations of the primary structures of plant proteins in relation to their anti-inflammatory, antimicrobial, antithrombotic and antitumoral properties. (AU)