Peptide/Peptoid Hybrid Oligomers: The Influence of Hydrophobicity and Relative Side-Chain Length on Antibacterial Activity and Cell Selectivity

Research output: Contribution to journalJournal articlepeer-review

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Peptide/Peptoid Hybrid Oligomers : The Influence of Hydrophobicity and Relative Side-Chain Length on Antibacterial Activity and Cell Selectivity. / Frederiksen, Nicki; Hansen, Paul R; Björkling, Fredrik; Franzyk, Henrik.

In: Molecules (Print Archive Edition), Vol. 24, 4429, 04.12.2019.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Frederiksen, N, Hansen, PR, Björkling, F & Franzyk, H 2019, 'Peptide/Peptoid Hybrid Oligomers: The Influence of Hydrophobicity and Relative Side-Chain Length on Antibacterial Activity and Cell Selectivity', Molecules (Print Archive Edition), vol. 24, 4429. https://doi.org/10.3390/molecules24244429

APA

Frederiksen, N., Hansen, P. R., Björkling, F., & Franzyk, H. (2019). Peptide/Peptoid Hybrid Oligomers: The Influence of Hydrophobicity and Relative Side-Chain Length on Antibacterial Activity and Cell Selectivity. Molecules (Print Archive Edition), 24, [4429]. https://doi.org/10.3390/molecules24244429

Vancouver

Frederiksen N, Hansen PR, Björkling F, Franzyk H. Peptide/Peptoid Hybrid Oligomers: The Influence of Hydrophobicity and Relative Side-Chain Length on Antibacterial Activity and Cell Selectivity. Molecules (Print Archive Edition). 2019 Dec 4;24. 4429. https://doi.org/10.3390/molecules24244429

Author

Frederiksen, Nicki ; Hansen, Paul R ; Björkling, Fredrik ; Franzyk, Henrik. / Peptide/Peptoid Hybrid Oligomers : The Influence of Hydrophobicity and Relative Side-Chain Length on Antibacterial Activity and Cell Selectivity. In: Molecules (Print Archive Edition). 2019 ; Vol. 24.

Bibtex

@article{3b9a59b775a04592b2ba432aafd47b0d,
title = "Peptide/Peptoid Hybrid Oligomers: The Influence of Hydrophobicity and Relative Side-Chain Length on Antibacterial Activity and Cell Selectivity",
abstract = "Previous optimisation studies of peptide/peptoid hybrids typically comprise comparison of structurally related analogues displaying different oligomer length and diverse side chains. The present work concerns a systematically constructed series of 16 closely related 12-mer oligomers with an alternating cationic/hydrophobic design, representing a wide range of hydrophobicity and differences in relative side-chain lengths. The aim was to explore and rationalise the structure-activity relationships within a subclass of oligomers displaying variation of three structural features: (i) cationic side-chain length, (ii) hydrophobic side-chain length, and (iii) type of residue that is of a flexible peptoid nature. Increased side-chain length of cationic residues led to reduced hydrophobicity till the side chains became more extended than the aromatic/hydrophobic side chains, at which point hydrophobicity increased slightly. Evaluation of antibacterial activity revealed that analogues with lowest hydrophobicity exhibited reduced activity against E. coli, while oligomers with the shortest cationic side chains were most potent against P. aeruginosa. Thus, membrane-disruptive interaction with P. aeruginosa appears to be promoted by a hydrophobic surface of the oligomers (comprised of the aromatic groups shielding the cationic side chains). Peptidomimetics with short cationic side chains exhibit increased hemolytic properties as well as give rise to decreased HepG2 (hepatoblastoma G2 cell line) cell viability. An optimal hydrophobicity window could be defined by a threshold of minimal hydrophobicity conferring activity toward E. coli and a threshold for maximal hydrophobicity, beyond which cell selectivity was lost.",
author = "Nicki Frederiksen and Hansen, {Paul R} and Fredrik Bj{\"o}rkling and Henrik Franzyk",
year = "2019",
month = dec,
day = "4",
doi = "10.3390/molecules24244429",
language = "English",
volume = "24",
journal = "Molecules (Print Archive Edition)",
issn = "1431-5157",
publisher = "M D P I AG",

}

RIS

TY - JOUR

T1 - Peptide/Peptoid Hybrid Oligomers

T2 - The Influence of Hydrophobicity and Relative Side-Chain Length on Antibacterial Activity and Cell Selectivity

AU - Frederiksen, Nicki

AU - Hansen, Paul R

AU - Björkling, Fredrik

AU - Franzyk, Henrik

PY - 2019/12/4

Y1 - 2019/12/4

N2 - Previous optimisation studies of peptide/peptoid hybrids typically comprise comparison of structurally related analogues displaying different oligomer length and diverse side chains. The present work concerns a systematically constructed series of 16 closely related 12-mer oligomers with an alternating cationic/hydrophobic design, representing a wide range of hydrophobicity and differences in relative side-chain lengths. The aim was to explore and rationalise the structure-activity relationships within a subclass of oligomers displaying variation of three structural features: (i) cationic side-chain length, (ii) hydrophobic side-chain length, and (iii) type of residue that is of a flexible peptoid nature. Increased side-chain length of cationic residues led to reduced hydrophobicity till the side chains became more extended than the aromatic/hydrophobic side chains, at which point hydrophobicity increased slightly. Evaluation of antibacterial activity revealed that analogues with lowest hydrophobicity exhibited reduced activity against E. coli, while oligomers with the shortest cationic side chains were most potent against P. aeruginosa. Thus, membrane-disruptive interaction with P. aeruginosa appears to be promoted by a hydrophobic surface of the oligomers (comprised of the aromatic groups shielding the cationic side chains). Peptidomimetics with short cationic side chains exhibit increased hemolytic properties as well as give rise to decreased HepG2 (hepatoblastoma G2 cell line) cell viability. An optimal hydrophobicity window could be defined by a threshold of minimal hydrophobicity conferring activity toward E. coli and a threshold for maximal hydrophobicity, beyond which cell selectivity was lost.

AB - Previous optimisation studies of peptide/peptoid hybrids typically comprise comparison of structurally related analogues displaying different oligomer length and diverse side chains. The present work concerns a systematically constructed series of 16 closely related 12-mer oligomers with an alternating cationic/hydrophobic design, representing a wide range of hydrophobicity and differences in relative side-chain lengths. The aim was to explore and rationalise the structure-activity relationships within a subclass of oligomers displaying variation of three structural features: (i) cationic side-chain length, (ii) hydrophobic side-chain length, and (iii) type of residue that is of a flexible peptoid nature. Increased side-chain length of cationic residues led to reduced hydrophobicity till the side chains became more extended than the aromatic/hydrophobic side chains, at which point hydrophobicity increased slightly. Evaluation of antibacterial activity revealed that analogues with lowest hydrophobicity exhibited reduced activity against E. coli, while oligomers with the shortest cationic side chains were most potent against P. aeruginosa. Thus, membrane-disruptive interaction with P. aeruginosa appears to be promoted by a hydrophobic surface of the oligomers (comprised of the aromatic groups shielding the cationic side chains). Peptidomimetics with short cationic side chains exhibit increased hemolytic properties as well as give rise to decreased HepG2 (hepatoblastoma G2 cell line) cell viability. An optimal hydrophobicity window could be defined by a threshold of minimal hydrophobicity conferring activity toward E. coli and a threshold for maximal hydrophobicity, beyond which cell selectivity was lost.

U2 - 10.3390/molecules24244429

DO - 10.3390/molecules24244429

M3 - Journal article

C2 - 31817108

VL - 24

JO - Molecules (Print Archive Edition)

JF - Molecules (Print Archive Edition)

SN - 1431-5157

M1 - 4429

ER -

ID: 231720485