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Synthesis, characterization, study of action mechanism and analysis of different release methods of pBthTX-I, in its monomeric and dimeric forms

Grant number: 14/05538-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2014
Effective date (End): February 28, 2018
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Eduardo Maffud Cilli
Grantee:Norival Alves Santos Filho
Home Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

Animals venoms and poisons are a rich source of pharmacologically active substances. These molecules act independently or synergistically, binding to different cellular receptors and/or in metabolic pathways. The exploration of the mechanisms of action of toxins has proved relevant, not only for providing the molecular basis involved in the mechanism of toxicity of these molecules , as well as enabling the application of toxins in the development of new therapeutic strategies . Infectious diseases are among the leading causes of death worldwide and the resistance of various strains of microorganisms in relation to their medications usually administered is a reality, increasing the search for new alternatives to antimicrobial compounds . Within this context , this proposal aims to study a peptide derived from the C-terminal region of PLA2 homologous Bothropstoxin I ( BthTX I - KKYRYHLKPFCKK ) , from Bothrops jararacuçu venom. Interestingly, previous studies have been performed with this peptide, both in its monomeric (p -BthTX -I) and dimeric [(p-BthTX-I)2] form, showing that they have specific activity against bacteria (both Gram positive and Gram negative), showing no toxicicidade against yeast and erythrocytes . Moreover , these molecules were not able to form pore or dissolve in membranes, indicating a mechanism of action remains unknown. Thus, the present work aims to study the mechanisms of action of the peptide based on the C - terminus of PLA2 homologous and analogous Bothropstoxin I region , as well as some dimeric forms , besides studying their structural and functional characteristics . Added to this , different mechanisms of release of peptides will be studied both in liquid crystalline system , as latex . (AU)

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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)
SANTOS-FILHO, NORIVAL A.; LORENZON, ESTEBAN N.; RAMOS, MATHEUS A. S.; SANTOS, CLAUDIA T.; PICCOLI, JULIA P.; BAUAB, TAIS M.; FUSCO-ALMEIDA, ANA M.; CILLI, EDUARDO M.. Synthesis and characterization of an antibacterial and non-toxic dimeric peptide derived from the C-terminal region of Bothropstoxin-I. Toxicon, v. 103, p. 160-168, . (14/05538-1)
SANTOS-FILHO, NORIVAL A.; FERNANDES, RAFAELA S.; SGARDIOLI, BRUNA F.; RAMOS, MATHEUS A. S.; PICCOLI, JULIA P.; CAMARGO, ILANA L. B. C.; BAUAB, TAIS M.; CILLI, EDUARDO M.. Antibacterial Activity of the Non-Cytotoxic Peptide (p-BthTX-I)(2) and Its Serum Degradation Product against Multidrug-Resistant Bacteria. Molecules, v. 22, n. 11, . (14/05538-1, 13/07600-3)
PINHEIRO-JUNIOR, ERNESTO LOPES; BOLDRINI-FRANCA, JOHARA; PIRES DE CAMPOS ARAUJO, LUCIANA MATTOSO; SANTOS-FILHO, NORIVAL ALVES; BENDHACK, LUSIANE MARIA; CILLI, EDUARDO MAFFUD; ARANTES, ELIANE CANDIANI. LmrBPP9: A synthetic bradykinin-potentiating peptide from Lachesis muta rhombeata venom that inhibits the angiotensin-converting enzyme activity in vitro and reduces the blood pressure of hypertensive rats. Peptides, v. 102, p. 1-7, . (14/05538-1, 14/16182-3, 13/07600-3)
SANTOS-FILHO, NORIVAL ALVES; DE FREITAS, LAURA MARISE; DOS SANTOS, CLAUDIA TAVARES; PICCOLI, JULIA PINTO; FONTANA, CARLA RAQUEL; FUSCO-ALMEIDA, ANA MARISA; CILLI, EDUARDO MAFFUD. nderstanding the mechanism of action of peptide (p-BthTX-I)(2) derived from C-terminal region of phospholipase A2 (PLA(2))-like bothropstoxin-I on Gram-positive and Gram-negative bacteri. Toxicon, v. 196, p. 44-55, . (14/05538-1, 14/24581-5, 13/07600-3)
SANTOS-FILHO, NORIVAL ALVES; RIGHETTO, GABRIELA MARINHO; PEREIRA, MARINA RODRIGUES; PICCOLI, JULIA PINTO; TEIZEN ALMEIDA, LARISSA MATHIAS; LEAL, THAINA CRISTINA; BARATELLA CUNHA CAMARGO, ILANA LOPES; CILLI, EDUARDO MAFFUD. Effect of C-terminal and N-terminal dimerization and alanine scanning on antibacterial activity of the analogs of the peptide p-BthTX-I. PEPTIDE SCIENCE, . (13/07600-3, 12/15346-7, 14/05538-1)

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