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

• Grant number: 19/22243-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2020
• End date: August 31, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Maria Luiza Vilela Oliva
• Grantee: Camila Ramalho Bonturi
• 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

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 legume 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)

Scientific publications

(5)

(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)

BONTURI, CAMILA RAMALHO; SILVA TEIXEIRA, ANA BEATRIZ; ROCHA, VITORIA MORAIS; VALENTE, PENELOPE FERREIRA; OLIVEIRA, JULIANA RODRIGUES; BEZERRA FILHO, CLOVIS MACEDO; DE FATIMA CORREIA BATISTA, ISABEL; OLIVA, MARIA LUIZA VILELA. Plant Kunitz Inhibitors and Their Interaction with Proteases: Current and Potential Pharmacological Targets. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 9, p. 19-pg., 2022-05-01. (17/06630-7, 19/22243-9)

OLIVA, MARIA LUIZA VILELA; DREVENY, INGRID; EMSLEY, JONAS. Exosites expedite blood coagulation. Journal of Biological Chemistry, v. 295, n. 45, p. 2-pg., 2020-11-06. (19/22243-9, 17/06630-7, 17/07972-9)

YOO IM, SONIA; RAMALHO BONTURI, CAMILA; MITI NAKAHATA, ADRIANA; RYUICHI NAKAIE, CLOVIS; POTT, ARNILDO; POTT, VALI JOANA; VILELA OLIVA, MARIA LUIZA. Differences in the Inhibitory Specificity Distinguish the Efficacy of Plant Protease Inhibitors on Mouse Fibrosarcoma. PLANTS-BASEL, v. 10, n. 3, MAR 2021. (17/07972-9, 17/06630-7, 19/22243-9)

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)

BONTURI, CAMILA RAMALHO; SALU, BRUNO RAMOS; BONAZZA, CAMILA NIMRI; SINIGAGLIA, RITA DE CASSIA; RODRIGUES, TIAGO; ALVAREZ-FLORES, MIRYAM PAOLA; CHUDZINSKI-TAVASSI, ANA MARISA; OLIVA, MARIA LUIZA VILELA. Proliferation and Invasion of Melanoma Are Suppressed by a Plant Protease Inhibitor, Leading to Downregulation of Survival/Death-Related Proteins. Molecules, v. 27, n. 9, p. 22-pg., 2022-05-01. (17/06630-7, 19/22243-9)