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Antimicrobial peptides: dimerization effects and encapsulation in NRLb biomembrane

Abstract

Given the increasing occurrence of pathogenic micro-organisms resistant to antibiotics, antimicrobial peptides (AMPs) appear as an interesting alternative, since they act through mechanisms of destruction of the cell membrane, in which hardly pathogens develop resistance. Many MAPs have been studied, but an accurate understanding of its molecular mechanism of action remains unclear. Recent researchs show that, regardless of the mechanism of action, the aggregation/oligomerization of AMPs is a prerequisite for the formation of pores. That is why it is suggested that self-association (oligomerization) of the AMPs have to be considered in the activity and selectivity of these molecules. Taking this into account, several AMPs have been dimerized getting some interesting pharmacotechnical advantages. However, the effect of dimerization on the biological activity is unclear, since some dimeric versions showed no greater activity, or were too toxic. Accordingly, monomeric and dimeric versions of three PAMs described in the literature and with different mechanisms of action will be syntesized. By spectroscopic techniques and biological assays will be assessed the influence of dimerization and polarity/length of the spacer between the peptide chains in the structure and biological activity of these molecules in order to understand in detail the relationship dimerization/mechanism of action. In addition, latex/PAMs conjugates will be synthetized and characterized and its properties, since liberation and toxicity evaluated. We believe that this knowledge can bring valuable information regarding the molecular basis of the mechanism of AMPs and thus contribute to the development of new antimicrobial agents. (AU)

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Scientific publications (9)
(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)
LORENZON, ESTEBAN N.; SANTOS-FILHO, NORIVAL A.; RAMOS, MATHEUS A. S.; BAUAB, TAIS M.; CAMARGO, ILANA L. B. C.; CILLI, EDUARDO M.. C-terminal Lysine-Linked Magainin 2 with Increased Activity Against Multidrug-Resistant Bacteria. PROTEIN AND PEPTIDE LETTERS, v. 23, n. 8, p. 738-747, . (12/15346-7, 13/07600-3)
LORENZON, E. N.; RISKE, K. A.; TROIANO, G. F.; DA HORA, G. C. A.; SOARES, T. A.; CILLI, E. M.. Effect of dimerization on the mechanism of action of aurein 1.2. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1858, n. 6, p. 1129-1138, . (12/15346-7, 12/10442-8)
MIRANDA, M. C. R.; BORGES, F. A.; BARROS, N. R.; SANTOS FILHO, N. A.; MENDONCA, R. J.; HERCULANO, R. D.; CILLI, E. M.. Evaluation of peptides release using a natural rubber latex biomembrane as a carrier. Amino Acids, v. 50, n. 5, p. 503-511, . (11/17411-8, 12/15346-7, 15/02343-8)
LORENZON, ESTEBAN N.; PICCOLI, JULIA P.; SANTOS-FILHO, NORIVAL A.; CILLI, EDUARDO M.. Dimerizatiori of Antimicrobial Peptides: A Promising Strategy to Enhance Antimicrobial Peptide Activity. PROTEIN AND PEPTIDE LETTERS, v. 26, n. 2, p. 98-107, . (12/15346-7, 13/07600-3)
CAIAFFA, KARINA SAMPAIO; MASSUNARI, LOIANE; DANELON, MARCELLE; ABUNA, GABRIEL FLORES; LOMBARDO BEDRAN, TELMA BLANCA; SANTOS-FILHO, NORIVAL ALVES; PALOMARI SPOLIDORIO, DENISE MADALENA; VIZOTO, NATALIA LEAL; CILLI, EDUARDO MAFFUD; DUQUE, CRISTIANE. KR-12-a5 is a non-cytotoxic agent with potent antimicrobial effects against oral pathogens. BIOFOULING, v. 33, n. 10, p. 807-818, . (12/15346-7, 13/24606-5)
LORENZON, ESTEBAN N.; PICCOLI, JULIA P.; CILLI, EDUARDO M.. Interaction between the antimicrobial peptide Aurein 1.2 dimer and mannans. Amino Acids, v. 46, n. 11, p. 2627-2631, . (12/15346-7)
INUI KISHI, ROSANGELA NAOMI; STACH-MACHADO, DAGMAR; SINGULANI, JUNYA DE LACORTE; DOS SANTOS, CLAUDIA TAVARES; FUSCO-ALMEIDA, ANA MARISA; CILLI, EDUARDO MAFFUD; FREITAS-ASTUA, JULIANA; PICCHI, SIMONE CRISTINA; MACHADO, MARCOS ANTONIO. Evaluation of cytotoxicity features of antimicrobial peptides with potential to control bacterial diseases of citrus. PLoS One, v. 13, n. 9, . (12/15346-7, 10/11072-4, 08/52691-9)
MIRANDA, M. C. R.; PREZOTTI, F. G.; BORGES, F. A.; BARROS, N. R.; CURY, B. S. F.; HERCULANO, R. D.; CILLI, E. M.. Porosity effects of natural latex (Hevea brasiliensis) on release of compounds for biomedical applications. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, v. 28, n. 18, p. 2117-2130, . (11/17411-8, 12/15346-7, 15/02343-8)
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)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.
Filed patent(s) as a result of this research project

PEPTÍDEO SINTÉTICO DIMÉRICO ANTIMICROBIANO E ANTIFÚNGICO E SEUS USOS BR1020140217614 - Universidade Estadual Paulista (UNESP) . Esteban Nicolás Lorenzon; Eduardo Maffud Cilli; Matheus Aparecido dos Santos Ramos; Taís Maria Bauab - September 2014, 03

PROCESSO DE OBTENÇÃO DE PEPTÍDEOS DIMÉRICOS (p-BthTX-I)2, PEPTÍDEOS DIMÉRICOS (p-BthTX-I)2 E SEU USO COMO ANTIMICROBIANO BR1020140315829 - Universidade Estadual Paulista (UNESP) . Esteban Nicolás Lorenzón; Eduardo Maffud Cilli; Matheus Aparecido dos Santos Ramos; Norival Alves Santos Filho; Taís Maria Bauab - December 2014, 17

PROCESSO DE OBTENÇÃO DE MEMBRANA POROSA DE LÁTEX NATURAL, MEMBRANA POROSA DE LÁTEX NATURAL E SEUS USOS BR1020150320477 - Universidade Estadual Paulista (UNESP) . Eduardo Maffud Cilli; Rondinelli Donizetti Herculano; Matheus Carlos Romeiro Miranda - December 2015, 21

Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação BR1020180719149 - Universidade Estadual Paulista (UNESP) . Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação - October 2018, 24

Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação PCT/BR2016/050337 - Universidade Estadual Paulista (UNESP) . Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação - December 2016, 19