Hydrophobic Control of the Bioactivity and Cytotoxicity of de Novo-Designed Antimicrobial PeptidesCitation formats

  • External authors:
  • Haoning Gong
  • Jing Zhang
  • Xuzhi Hu
  • Zongyi Li
  • Ke Fa
  • Huayang Liu

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Hydrophobic Control of the Bioactivity and Cytotoxicity of de Novo-Designed Antimicrobial Peptides. / Gong, Haoning; Zhang, Jing; Hu, Xuzhi; Li, Zongyi; Fa, Ke; Liu, Huayang; Waigh, Thomas A.; Mcbain, Andrew; Lu, Jian Ren.

In: ACS applied materials & interfaces, 2019.

Research output: Contribution to journalArticle

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Gong H, Zhang J, Hu X, Li Z, Fa K, Liu H et al. Hydrophobic Control of the Bioactivity and Cytotoxicity of de Novo-Designed Antimicrobial Peptides. ACS applied materials & interfaces. 2019. https://doi.org/10.1021/acsami.9b10028

Author

Gong, Haoning ; Zhang, Jing ; Hu, Xuzhi ; Li, Zongyi ; Fa, Ke ; Liu, Huayang ; Waigh, Thomas A. ; Mcbain, Andrew ; Lu, Jian Ren. / Hydrophobic Control of the Bioactivity and Cytotoxicity of de Novo-Designed Antimicrobial Peptides. In: ACS applied materials & interfaces. 2019.

Bibtex

@article{559835be6ce4431398492bde7fdbcca6,
title = "Hydrophobic Control of the Bioactivity and Cytotoxicity of de Novo-Designed Antimicrobial Peptides",
abstract = "Antimicrobial peptides (AMPs) can target bacterial membranes and kill bacteria through membrane structural damage and cytoplasmic leakage. A group of surfactant-like cationic AMPs was developed from substitutions to selective amino acids in the general formula of G(IIKK)3I-NH2, (called G3, a de novo AMP), to explore the correlation between AMP hydrophobicity and bioactivity. A threshold surface pressure over 12 mN/m was required to cause measurable antimicrobial activity and this corresponded to a critical AMP concentration. Greater surface activity exhibited stronger antimicrobial activity but had the drawback of worsening hemolytic activity. Small unilamellar vesicles (SUVs) with specific lipid compositions were used to model bacterial and host mammalian cell membranes by mimicking the main structural determinants of the charge and composition. Leakage from the SUVs of encapsulated carboxyfluorescein measured by fluorescence spectroscopy indicated a negative correlation between hydrophobicity and model membrane selectivity, consistent with measurements of the zeta potential that demonstrated the extent of AMP binding onto model SUV lipid bilayers. Experiments with model lipid membranes thus explained the trend of minimum inhibitory concentrations and selectivity measured from real cell systems and demonstrated the dominant influence of hydrophobicity. This work provides useful guidance for the improvement of the potency of AMPs via structural design, whilst taking due consideration of cytotoxicity.",
keywords = "antimicrobial peptides, peptide design, antimicrobial resistance, membrane hemolysis, hydrophobicity, bioactivity, biocompatibility",
author = "Haoning Gong and Jing Zhang and Xuzhi Hu and Zongyi Li and Ke Fa and Huayang Liu and Waigh, {Thomas A.} and Andrew Mcbain and Lu, {Jian Ren}",
year = "2019",
doi = "10.1021/acsami.9b10028",
language = "English",
journal = "A C S Applied Materials and Interfaces",
issn = "1944-8244",
publisher = "American Chemical Society",

}

RIS

TY - JOUR

T1 - Hydrophobic Control of the Bioactivity and Cytotoxicity of de Novo-Designed Antimicrobial Peptides

AU - Gong, Haoning

AU - Zhang, Jing

AU - Hu, Xuzhi

AU - Li, Zongyi

AU - Fa, Ke

AU - Liu, Huayang

AU - Waigh, Thomas A.

AU - Mcbain, Andrew

AU - Lu, Jian Ren

PY - 2019

Y1 - 2019

N2 - Antimicrobial peptides (AMPs) can target bacterial membranes and kill bacteria through membrane structural damage and cytoplasmic leakage. A group of surfactant-like cationic AMPs was developed from substitutions to selective amino acids in the general formula of G(IIKK)3I-NH2, (called G3, a de novo AMP), to explore the correlation between AMP hydrophobicity and bioactivity. A threshold surface pressure over 12 mN/m was required to cause measurable antimicrobial activity and this corresponded to a critical AMP concentration. Greater surface activity exhibited stronger antimicrobial activity but had the drawback of worsening hemolytic activity. Small unilamellar vesicles (SUVs) with specific lipid compositions were used to model bacterial and host mammalian cell membranes by mimicking the main structural determinants of the charge and composition. Leakage from the SUVs of encapsulated carboxyfluorescein measured by fluorescence spectroscopy indicated a negative correlation between hydrophobicity and model membrane selectivity, consistent with measurements of the zeta potential that demonstrated the extent of AMP binding onto model SUV lipid bilayers. Experiments with model lipid membranes thus explained the trend of minimum inhibitory concentrations and selectivity measured from real cell systems and demonstrated the dominant influence of hydrophobicity. This work provides useful guidance for the improvement of the potency of AMPs via structural design, whilst taking due consideration of cytotoxicity.

AB - Antimicrobial peptides (AMPs) can target bacterial membranes and kill bacteria through membrane structural damage and cytoplasmic leakage. A group of surfactant-like cationic AMPs was developed from substitutions to selective amino acids in the general formula of G(IIKK)3I-NH2, (called G3, a de novo AMP), to explore the correlation between AMP hydrophobicity and bioactivity. A threshold surface pressure over 12 mN/m was required to cause measurable antimicrobial activity and this corresponded to a critical AMP concentration. Greater surface activity exhibited stronger antimicrobial activity but had the drawback of worsening hemolytic activity. Small unilamellar vesicles (SUVs) with specific lipid compositions were used to model bacterial and host mammalian cell membranes by mimicking the main structural determinants of the charge and composition. Leakage from the SUVs of encapsulated carboxyfluorescein measured by fluorescence spectroscopy indicated a negative correlation between hydrophobicity and model membrane selectivity, consistent with measurements of the zeta potential that demonstrated the extent of AMP binding onto model SUV lipid bilayers. Experiments with model lipid membranes thus explained the trend of minimum inhibitory concentrations and selectivity measured from real cell systems and demonstrated the dominant influence of hydrophobicity. This work provides useful guidance for the improvement of the potency of AMPs via structural design, whilst taking due consideration of cytotoxicity.

KW - antimicrobial peptides

KW - peptide design

KW - antimicrobial resistance

KW - membrane hemolysis

KW - hydrophobicity

KW - bioactivity

KW - biocompatibility

U2 - 10.1021/acsami.9b10028

DO - 10.1021/acsami.9b10028

M3 - Article

JO - A C S Applied Materials and Interfaces

JF - A C S Applied Materials and Interfaces

SN - 1944-8244

ER -