Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Volume 1858, Issue 7, Pages 1488-1498Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2016.04.003
Keywords
Pleuronectes americanus; Synthetic palindromic peptide; Pa-MAP2; Secondary structure; Molecular dynamics
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Funding
- Brazilian funding agency CNPq
- Brazilian funding agency CAPES
- Brazilian funding agency FADPDF
- Brazilian funding agency FINEP
- Brazilian funding agency FUNDECT
- Fundacao para a Ciencia e a Tecnologia - Ministerio da Ciencia, Tecnologia e Ensino Superior (FCT-MCTES, Portugal)
- Marie Sktodowska-Curie Research and Innovation Staff Exchange (MSCA-RISE, European Union) project INPACT (H2020-MSCA-RISE) [644167]
- FCT-MCTES fellowship [SPRH/BD/100517/2014]
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Recently, several peptides have been studied regarding the defence process against pathogenic microorganisms, which are able to act against different targets, with the purpose of developing novel bioactive compounds. The present work focuses on the structural and functional evaluation of the palindromic antimicrobial peptide Pa-MAP2, designed based on the peptide Pa-MAP from Pleuronectes americanus. For a better structural understanding, molecular modelling analyses were carried out, together with molecular dynamics and circular dichroism, in different media. Antibacterial activity against Gram-negative and positive bacteria was evaluated, as well as cytotoxicity against human erythrocytes, RAW 264.7, Vero and L6 cells. In silico docking experiments, lipid vesicle studies, and atomic force microscopy (AFM) imaging were carried out to explore the activity of the peptide. In vivo studies on infected mice were also done. The palindromic primary sequence favoured an of alpha-helix structure that was pH dependent, only present on alkaline environment, with dynamic N- and C-terminals that are stabilized in anionic media. Pa-MAP2 only showed activity against Gram-negative bacteria, with a MIC of 3.2 mu M, and without any cytotoxic effect. In silico, lipid vesicles and AFM studies confirm the preference for anionic lipids (POPG, POPS, DPPE, DPPG and LPS), with the positively charged lysine residues being essential for the initial electrostatic interaction. In vivo studies showed that Pa-MAP2 increases to 100% the survival rate of mice infected with Escherichia coli. Data here reported indicated that palindromic Pa-MAP2 could be an alternative candidate for use in therapeutics against Gram-negative bacterial infections. (C) 2016 Published by Elsevier B.V.
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