Structure-Activity Relationship of the Antimicrobial Peptide Gomesin: the Role of Peptide Hydrophobicity in Its Interaction with Model Membranes

Structure-Activity Relationship of the Antimicrobial Peptide Gomesin: the Role of Peptide Hydrophobicity in Its Interaction with Model Membranes

Author Mattei, Bruno Autor UNIFESP Google Scholar
Miranda, Antonio Autor UNIFESP Google Scholar
Perez, Katia R. Autor UNIFESP Google Scholar
Riske, Karin A. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Antimicrobial peptides are part of the innate immune system of animals and plants. Their lytic activity against microorganisms generally depends on their ability to disrupt and permeabilize membranes. Here we study the structure activity relationship of the antimicrobial peptide gomesin (Gm), from the spider Acanthoscurria gomesiana, with large unilamellar vesicles (LUVs) composed of 3:7 palmitoyloleoyl phosphatidylglycerol: palmitoyloleoyl phosphatidylcholine. Several synthetic analogues of Gm were designed to alter the hydrophobicity/charge of the molecule, whereby selected amino acid residues were replaced by alanine. Isothermal titration calorimetry (ITC) was used to assess the thermodynamic parameters of peptide binding to LUVs and light scattering measurements were made to evaluated peptide-induced vesicle aggregation. the ability of the peptides to permeabilize vesicles was quantified through the leakage of an entrapped fluorescent probe. the activity of peptides could be quantified in terms of the leakage extent induced and their affinity to the membrane, which was largely dictated by the exothermic enthalpy change. the results show that analogues more hydrophobic than Gm display higher activity, whereas peptides more hydrophilic than Gm have their activity almost abolished. Vesicle aggregation, on the other hand, largely increases with peptide charge. We conclude that interaction of Gm with membranes depends on an interplay between surface electrostatic interactions, which drive anchoring to the membrane surface and vesicle aggregation, and insertion of the hydrophobic portion into the membrane core, responsible for causing membrane rupture/permeabilization.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
INCT-FCx
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Date 2014-04-01
Published in Langmuir. Washington: Amer Chemical Soc, v. 30, n. 12, p. 3513-3521, 2014.
ISSN 0743-7463 (Sherpa/Romeo, impact factor)
Publisher Amer Chemical Soc
Extent 3513-3521
Origin http://dx.doi.org/10.1021/la500146j
Access rights Closed access
Type Article
Web of Science ID WOS:000333776400029
URI http://repositorio.unifesp.br/handle/11600/37634

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