Mechanism of action of Enterolobium contortisiliquum-derived mimetic peptides on platelet signaling and function

• Grant number: 20/01512-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2020
• End date: February 28, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Maria Luiza Vilela Oliva
• Grantee: Ruben Siedlarczyk Nogueira
• Host Institution: Escola Paulista de Medicina (EPM). 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

Abstract

Thromboembolic events remain the leading cause of death worldwide. In Brazil, WHO data point to cardiovascular diseases caused by 28% of deaths in 2016, representing a serious public health problem. Platelets are cells derived from the cytoplasmic fragmentation of megakaryocytes and protagonists in the hemostatic process. Its role in the body is increasingly studied, both in hemostasis and in the immunity of inflammatory and infectious processes, and the activity of these cells is regulated by complex and sometimes poorly understood signaling pathways. Thus, understanding these signaling pathways is important and can culminate in the establishment of new therapeutic targets to control these diseases. Our group has been isolating and characterizing proteolytic enzyme inhibitors for the past 20 years, finishing with a structural, functional and biochemical characterization of an inhibitor isolated from Enterolobium contortisiliquum seeds - EcTI. From the primary sequence of this inhibitor, a synthetic peptide was obtained and it plays a direct role on platelets and on the hemostatic system, increasing the formation time of arterial thrombi in mice, as well as inhibiting an ADP-stimulated platelet aggregation. However, we still do not know the mechanism of action of this peptide. Therefore, we intend, through molecular studies of signaling by immunoblotting, ELISA and transmission electron microscopy, combined with functional assays of platelet aggregation and adhesion, to determine which form this peptide is able to affect function and platelet molecular events. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NOGUEIRA, RUBEN SIEDLARCZYK; SALU, BRUNO RAMOS; NARDELLI, VINICIUS GOULART; BONTURI, CAMILA RAMALHO; PEREIRA, MARINA RODRIGUES; MAFFEI, FRANCISCO HUMBERTO DE ABREU; CILLI, EDUARDO MAFFUD; OLIVA, MARIA LUIZA VILELA. A snake venom-analog peptide that inhibits SARS-CoV-2 and papain-like protease displays antithrombotic activity in mice arterial thrombosis model, without interfering with bleeding time. THROMBOSIS JOURNAL, v. 21, n. 1, p. 10-pg., 2023-01-02. (17/06630-7, 20/05761-3, 19/22243-9, 20/01512-9)