Publicação
Structural and functional evaluation of the palindromic alanine-rich antimicrobial peptide Pa-MAP2
| dc.contributor.author | Migliolo, Ludovico | |
| dc.contributor.author | Felício, Mário Romão | |
| dc.contributor.author | Cardoso, Marlon H. | |
| dc.contributor.author | Silva, Osmar N. | |
| dc.contributor.author | Xavier, Mary-Ann E. | |
| dc.contributor.author | Nolasco, Diego O. | |
| dc.contributor.author | Oliveira, Adeliana Silva de | |
| dc.contributor.author | Roca-Subira, Ignasi | |
| dc.contributor.author | Estape, Jordi Vila | |
| dc.contributor.author | Teixeira, Leandro D. | |
| dc.contributor.author | Freitas, Sonia M. | |
| dc.contributor.author | Otero-Gonzalez, Anselmo J. | |
| dc.contributor.author | Abreu, Sónia Gonçalves | |
| dc.contributor.author | Santos, Nuno | |
| dc.contributor.author | Franco, Octavio L. | |
| dc.date.accessioned | 2019-03-25T11:32:49Z | |
| dc.date.available | 2019-03-25T11:32:49Z | |
| dc.date.issued | 2016 | |
| dc.description | © 2016 Published by Elsevier B.V. | pt_PT |
| dc.description.abstract | 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 α-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 μM, 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. | pt_PT |
| dc.description.sponsorship | This work was supported by the Brazilian funding agencies CNPq, CAPES, FADPDF, FINEP and FUNDECT, by Fundação para a Ciência e a Tecnologia — Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), and by Marie Skłodowska-Curie Research and Innovation Staff Exchange (MSCA-RISE, European Union) project INPACT (call H2020-MSCA-RISE-2014, grant agreement 644167). MRF also acknowledges FCT-MCTES fellowship SPRH/BD/100517/2014. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Biochimica et Biophysica Acta 1858 (2016) 1488–1498 | pt_PT |
| dc.identifier.doi | 10.1016/j.bbamem.2016.04.003 | pt_PT |
| dc.identifier.issn | 0005-2736 | |
| dc.identifier.uri | http://hdl.handle.net/10451/37672 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Elsevier | pt_PT |
| dc.relation | 644167 | pt_PT |
| dc.relation | SPRH/BD/100517/2014 | pt_PT |
| dc.relation.publisherversion | https://www.sciencedirect.com/journal/biochimica-et-biophysica-acta-bba-biomembranes | pt_PT |
| dc.subject | Pleuronectes americanus | pt_PT |
| dc.subject | Synthetic palindromic peptide | pt_PT |
| dc.subject | Pa-MAP2 | pt_PT |
| dc.subject | Secondary structure | pt_PT |
| dc.subject | Molecular dynamics | pt_PT |
| dc.title | Structural and functional evaluation of the palindromic alanine-rich antimicrobial peptide Pa-MAP2 | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 1498 | pt_PT |
| oaire.citation.issue | 1858 | pt_PT |
| oaire.citation.startPage | 1488 | pt_PT |
| oaire.citation.title | Biochimica et Biophysica Acta (BBA) - Biomembranes | pt_PT |
| person.familyName | Romão Felício | |
| person.familyName | Abreu | |
| person.familyName | Santos | |
| person.givenName | Mário | |
| person.givenName | Sónia | |
| person.givenName | Nuno | |
| person.identifier | 384205 | |
| person.identifier.ciencia-id | F811-74AE-412A | |
| person.identifier.ciencia-id | CD13-5E3A-A3C5 | |
| person.identifier.orcid | 0000-0002-9398-2140 | |
| person.identifier.orcid | 0000-0003-2903-4282 | |
| person.identifier.orcid | 0000-0002-0580-0475 | |
| person.identifier.rid | J-8517-2014 | |
| person.identifier.rid | H-9482-2017 | |
| person.identifier.rid | N-7248-2013 | |
| person.identifier.scopus-author-id | 57144367400 | |
| person.identifier.scopus-author-id | 35602210000 | |
| person.identifier.scopus-author-id | 55940818300 | |
| rcaap.rights | restrictedAccess | pt_PT |
| rcaap.type | article | pt_PT |
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