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The use of fragments derived from the structure of protease inhibitors isolated from legumes with antithrombotic properties: mechanism of action

Grant number: 18/07299-5
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2018
Effective date (End): March 13, 2022
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:Maria Luiza Vilela Oliva
Grantee:Bruno Ramos Salu
Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:17/06630-7 - 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, AP.TEM


Our laboratory has been isolating and characterizing numerous inhibitors of plant origin, with action on different proteases of the coagulation cascade, proteases released by leukocytes or that which interfere with platelet aggregation. Some of these inhibitors showed antithrombotic action in different experimental models of Arterial and Venous Thrombosis, with little or no interference in coagulation tests or bleeding time (Brito et al., 2014), suggesting that they are substances which could have a potential therapeutic value, inhibiting the development of Thromboses with a lower hemorrhagic effect. The Crataeva tapia Bark Lectin (CrataBL) and EcTI, from Enterolobium contortisiliquum seeds, by inhibiting the molecular pathways of inflammation, becoming very interesting to investigate its effects in an experimental model of murine lower limb ischemia in vivo.The present study aims the use of synthetic peptides derived from proteins previously identified with antithrombotic efficacy, aiming: 1) to identify and characterize blood coagulation proteases as potential targets of peptide inhibitors; 2) to evaluate the effect on blood coagulation parameters; 3) to study the effect in platelet aggregation; 4) to investigate the mechanism of action of peptides in signal transduction pathways and in the cascade of activation of proteases involved in Thrombosis and hemostasis and lower limb ischemia; 5) to carry out structural modifications of the peptides investigating the effects on solubility and resistance to proteolysis. In this way, the development of this project could result in the identification of compounds with great clinical importance in the prophylaxis and treatment of thrombotic diseases and offers new opportunities for therapeutic intervention with possibilities of development biotechnological products. (AU)

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