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Prediction of Antibacterial Activity from Physicochemical Properties of Antimicrobial Peptides

Consensus is gathering that antimicrobial peptides that exert their antibacterial action at the membrane level must reach a local concentration threshold to become active. Studies of peptide interaction with model membranes do identify such disruptive thresholds but demonstrations of the possible correlation of these with the in vivo onset of activity have only recently been proposed. In addition, such thresholds observed in model membranes occur at local peptide concentrations close to full membrane coverage. In this work we fully develop an interaction model of antimicrobial peptides with biological membranes; by exploring the consequences of the underlying partition formalism we arrive at a relationship that provides antibacterial activity prediction from two biophysical parameters: the affinity of the peptide to the membrane and the critical bound peptide to lipid ratio. A straightforward and robust method to implement this relationship, with potential application to high-throughput screening approaches, is presented and tested. In addition, disruptive thresholds in model membranes and the onset of antibacterial peptide activity are shown to occur over the same range of locally bound peptide concentrations (10 to 100 mM), which conciliates the two types of observations

PLoS ONE, 2012, vol. 6, núm. 12, p. e28549

Public Library of Science

Author: Melo, Manuel N.
Ferre Malagon, Rafael
Feliu Soley, Lídia
Bardají Rodríguez, Eduard
Planas i Grabuleda, Marta
Castanho, Miguel Augusto Rico Botas
Date: 2011 December
Abstract: Consensus is gathering that antimicrobial peptides that exert their antibacterial action at the membrane level must reach a local concentration threshold to become active. Studies of peptide interaction with model membranes do identify such disruptive thresholds but demonstrations of the possible correlation of these with the in vivo onset of activity have only recently been proposed. In addition, such thresholds observed in model membranes occur at local peptide concentrations close to full membrane coverage. In this work we fully develop an interaction model of antimicrobial peptides with biological membranes; by exploring the consequences of the underlying partition formalism we arrive at a relationship that provides antibacterial activity prediction from two biophysical parameters: the affinity of the peptide to the membrane and the critical bound peptide to lipid ratio. A straightforward and robust method to implement this relationship, with potential application to high-throughput screening approaches, is presented and tested. In addition, disruptive thresholds in model membranes and the onset of antibacterial peptide activity are shown to occur over the same range of locally bound peptide concentrations (10 to 100 mM), which conciliates the two types of observations
Format: application/pdf
ISSN: 1932-6203
Document access: http://hdl.handle.net/10256/7786
Language: eng
Publisher: Public Library of Science
Collection: Reproducció digital del document publicat a: http://dx.doi.org/10.1371/journal.pone.0028549
Articles publicats (D-Q)
Is part of: PLoS ONE, 2012, vol. 6, núm. 12, p. e28549
Rights: Attribution 3.0 Spain
Rights URI: http://creativecommons.org/licenses/by/3.0/es/
Subject: Antibiòtics pèptids
Peptide antibiotics
Fisicoquímica
Chemistry, Physical and theorical
Bacteris
Bacteria
Title: Prediction of Antibacterial Activity from Physicochemical Properties of Antimicrobial Peptides
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

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