Structural and functional studies with Bothropstoxin-I, from Bothrops jararacussu snake venom, and caffeic acid derivates

• Grant number: 12/07112-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2012
• Effective date (End): February 29, 2016
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Marcos Roberto de Mattos Fontes
• Grantee: Fábio Florença Cardoso
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 08/57898-0 - National Institute of Science and Technology on Toxins, AP.TEM

Abstract

Envenoming involving Bothrops snakes stand out in Brazil and other Latin American countries, representing 90% of notifications. Botropic envenoming is characterized by intense local myonecrosis that is not effectlively neutralized by the only available treatment, i.e., the antivenom. As a result, in severe cases, this envenoming can lead to amputation of limbs, disabling the victim. The main responsibles for the myonecrosis development are proteins structurally similar to phospholipase A2 enzymes (PLA2s). Among these PLA2s, stand out the catalytically inactive variants that have a lysine residue at position 49 (Lys49-PLA2s). Thus, it is proposed the study structural of bothropstoxin-I (BthTX-I), a Lys49-PLA2 isolated from Bothrops jararacussu, by techniques of X-ray crystallography. In this study, we propose the study of the interaction between the BthTX-I and possible inhibitors, such as cinnamic acid, p-coumarin acid, ferulic acid, chlorogenic acid, caftaric acid and cichoric acid. Corroboration of the neutralizing activity of these inhibitors will be investigated by electrophysiological and morphological studies in mice neuromuscular preparations. This project is the continuation of studies performed by the candidate in his master's course, that investigated the role of compounds of similar origin to those proposed in this project in the activity of the PrTX-I, a toxin almost identical to BthTX-I. The results of these studies were published in an international journal of high impact and two others articles are currently in preparation.

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)

CARDOSO, FABIO F.; DE SOUZA, MAXIMILIA F.; OLIVEIRA, CRISTIANO L. P.; FONTES, MARCOS R. M.. In-solution structural studies involving a phospholipase A 2-like myotoxin and a natural inhibitor: Plasticity of oligomeric assembly affects mechanisms of inhibition. Biochimie, v. 181, p. 145-153, FEB 2021. (15/17286-0, 12/07112-6, 18/16092-5)

CARDOSO, FABIO F.; GOMES, ANTONIEL A. S.; DREYER, THIAGO R.; CAVALCANTE, WALTER L. G.; DAL PAI, MAELI; GALLACCI, MARCIA; FONTES, MARCOS R. M.. Neutralization of a bothropic PLA(2)-like protein by caftaric acid, a novel potent inhibitor of ophidian myotoxicity. Biochimie, v. 170, p. 163-172, MAR 2020. (12/07112-6, 15/17286-0)

CARDOSO, FABIO F.; BORGES, RAFAEL J.; DREYER, THIAGO R.; SALVADOR, GUILHERME H. M.; CAVALCANTE, WALTER L. G.; DAL PAI, MAELI; GALLACCI, MARCIA; FONTES, MARCOS R. M.. Structural basis of phospholipase A(2)-like myotoxin inhibition by chicoric acid, a novel potent inhibitor of ophidian toxins. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1862, n. 12, p. 2728-2737, DEC 2018. (15/17286-0, 12/07112-6)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CARDOSO, Fábio Florença. Structural and functional studies of interaction between cinnamic acid derivatives and phospholipase A2-like myotoxin from Bothrops jararacussu snake venom. 2016. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.