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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The ``pre-assembled state{''} of magainin 2 lysine-linked dimer determines its enhanced antimicrobial activity

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Autor(es):
Lorenzon, Esteban N. [1, 2] ; Nobre, Thatyane M. [1] ; Caseli, Luciano [3] ; Cilli, Eduardo M. [4] ; da Hora, Gabriel C. A. [5] ; Soares, Thereza A. [5] ; Oliveira, Jr., Osvaldo N. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos, SP - Brazil
[2] Univ Fed Goias, Inst Ciencias Biol, Dept Bioquim & Biol Mol, ICB 2 Sala 118, Campus 2 Samambaia, BR-74690900 Goiania, Go - Brazil
[3] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP - Brazil
[4] Univ Estadual Paulista, Inst Quim, Araraquara, SP - Brazil
[5] Univ Fed Pernambuco, Dept Quim Fundamental, Recife, PE - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: COLLOIDS AND SURFACES B-BIOINTERFACES; v. 167, p. 432-440, JUL 1 2018.
Citações Web of Science: 0
Resumo

Antimicrobial peptides (AMPs) are alternatives to conventional antibiotics against multi-drug resistant bacteria with low potential for developing microbial resistance. The design of such molecules requires understanding of the mechanisms of action, particularly the interaction with bacteria cell membranes. In this work, we determine the mechanism responsible for the higher activity against Escherichia coil of the C-terminal lysine dimer of magainin 2, (MG2)(2)K, in comparison to the monomeric peptide magainin 2 (MG2). Langmuir monolayers and vesicles made with the E. coli lipid extract were used to address the two possible states for the peptide-membrane interaction, namely the ``binding state{''} and ``pore state{''}, respectively. The incorporation of MG2 and (MG2)(2)K in lipid monolayers at the air-water interface caused slight differences in surface pressure isotherms and polarization-modulated infrared reflection absorption (PM-IRRAS) spectra, and therefore the difference in activity is not associated with the binding state. In contrast, large differences were observed in the leakage experiments where (MG2)(2)K was shown to disrupt the large unilamellar vesicles to a much higher extent owing to efficient pore formation. The binding and penetration of MG2 and (MG2)(2)K were also probed with molecular dynamics (MD) simulations for bilayers made with 1-palmitoy1-2-oleoyl-sn-g/ycero-3-phosphoethanolamine:1-palmitoy1-2-oleo yl-snglycero-3-phosphoglycerol (POPE:POPG). (MG2)(2)K forms disordered toroidal pores at a significant lower concentration than for MG2. In summary, the combination of experimental and computational simulation results indicated that the ``pre-assembling state{''} of (MG2)(2)K dimer leads to a reduced number of molecules and shorter time being required to kill E. coli. (C) 2018 Elsevier B.V. All rights reserved. (AU)

Processo FAPESP: 13/14262-7 - Filmes nanoestruturados de materiais de interesse biológico
Beneficiário:Osvaldo Novais de Oliveira Junior
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 15/16857-3 - Uso de modelos de membrana para estudar o mecanismo de ação de peptídeos antimicrobianos e efeitos da dimerização e ciclização
Beneficiário:Esteban Nicolás Lorenzón
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
Beneficiário:Glaucius Oliva
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs