Self-Assembly, Antimicrobial Activity, and Membrane Interactions of Arginine-Capped Peptide Bola-Amphiphiles

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Volume Title

A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Date

2019-05-20

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Language

en

Pages

11
2208-2218

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ACS Applied Bio Materials, Volume 2, issue 5

Abstract

The self-assembly and antimicrobial activity of two novel arginine-capped bola-amphiphile peptides, namely RA6R and RA9R (R, arginine; A, alanine) are investigated. RA6R does not self-assemble in water due to its high solubility, but RA9R self-assembles above a critical aggregation concentration into ordered nanofibers due to the high hydrophobicity of the A9block. The structure of the RA9R nanofibers is studied by cryogenic transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS). Circular dichroism spectroscopy shows that both RA6R and RA9R adopt coil conformations in water at low concentration, but only RA9R adopts a β-sheet conformation at high concentration. SAXS and differential scanning calorimetry are used to study RA6R and RA9R interactions with a mixed lipid membrane that models a bacterial cell wall, consisting of multilamellar 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine vesicles. Cytotoxicity studies show that RA6R is more cytocompatible than RA9R. RA6R has enhanced activity against the Gram-negative pathogen P. aeruginosa at a concentration where viability of mammalian cells is retained. RA9R has little antimicrobial activity, independently of concentration. Our results highlight the influence of the interplay between relative charge and hydrophobicity on the self-assembly, cytocompatibility, and bioactivity of peptide bola-amphiphiles.

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Keywords

antibacterials, antimicrobial peptides, lipid membranes, peptides, self-assembly

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Citation

Edwards-Gayle, C J C, Castelletto, V, Hamley, I W, Barrett, G, Greco, F, Hermida-Merino, D, Rambo, R P, Seitsonen, J & Ruokolainen, J 2019, ' Self-Assembly, Antimicrobial Activity, and Membrane Interactions of Arginine-Capped Peptide Bola-Amphiphiles ', ACS Applied Bio Materials, vol. 2, no. 5, pp. 2208-2218 . https://doi.org/10.1021/acsabm.9b00172