Lysine-Based α-peptide/β-peptoid peptidomimetics: Influence of hydrophobicity, fluorination and distribution of cationic charge on antimicrobial activity and cytotoxicity

Natalia Molchanova; Paul Robert Hansen; Peter Panduro Damborg; Hanne Mørck Nielsen; Henrik Franzyk

doi:10.1002/cmdc.201600553

Lysine-Based α-peptide/β-peptoid peptidomimetics: Influence of hydrophobicity, fluorination and distribution of cationic charge on antimicrobial activity and cytotoxicity

Natalia Molchanova, Paul Robert Hansen, Peter Panduro Damborg, Hanne Mørck Nielsen, Henrik Franzyk

27 Citations (Scopus)

Abstract

Multidrug-resistant bacteria pose a serious threat to public health worldwide. Previously, α-peptide/β-peptoid hybrid oligomers were found to display activity against Gram-negative multidrug-resistant bacteria. In the present work, the influence of hydrophobicity, fluorination, and distribution of cationic/hydrophobic residues on antimicrobial, hemolytic, and cytotoxic properties of α-peptide/β-peptoid hybrids were investigated. An array of 22 peptidomimetics was tested. Analogues with enhanced hydrophobicity were found to exhibit increased activity against Gram-positive bacteria. Incorporation of fluorinated residues into the peptidomimetics conferred increased potency against Gram-positive bacteria, while hemolytic properties and activity against Gram-negative bacteria depended on the degree and type of fluorination. Generally, shorter oligomers were less potent than the corresponding longer analogues. However, some short analogues exhibited equal or higher antimicrobial activity. The alternating hydrophobic/cationic design proved superior to other distribution patterns of cationic side chains and hydrophobic moieties.

Original language	English
Journal	ChemMedChem
Volume	12
Pages (from-to)	312-318
Number of pages	7
ISSN	1860-7179
DOIs	https://doi.org/10.1002/cmdc.201600553
Publication status	Published - 20 Feb 2017

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Lysine-Based α-peptide/β-peptoid peptidomimetics: Influence of hydrophobicity, fluorination and distribution of cationic charge on antimicrobial activity and cytotoxicity. / Molchanova, Natalia; Hansen, Paul Robert ; Damborg, Peter Panduro et al.
In: ChemMedChem, Vol. 12, 20.02.2017, p. 312-318.

Research output: Contribution to journal › Journal article › Research › peer-review

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abstract = "Multidrug-resistant bacteria pose a serious threat to public health worldwide. Previously, α-peptide/β-peptoid hybrid oligomers were found to display activity against Gram-negative multidrug-resistant bacteria. In the present work, the influence of hydrophobicity, fluorination, and distribution of cationic/hydrophobic residues on antimicrobial, hemolytic, and cytotoxic properties of α-peptide/β-peptoid hybrids were investigated. An array of 22 peptidomimetics was tested. Analogues with enhanced hydrophobicity were found to exhibit increased activity against Gram-positive bacteria. Incorporation of fluorinated residues into the peptidomimetics conferred increased potency against Gram-positive bacteria, while hemolytic properties and activity against Gram-negative bacteria depended on the degree and type of fluorination. Generally, shorter oligomers were less potent than the corresponding longer analogues. However, some short analogues exhibited equal or higher antimicrobial activity. The alternating hydrophobic/cationic design proved superior to other distribution patterns of cationic side chains and hydrophobic moieties.",

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AU - Nielsen, Hanne Mørck

AU - Franzyk, Henrik

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AB - Multidrug-resistant bacteria pose a serious threat to public health worldwide. Previously, α-peptide/β-peptoid hybrid oligomers were found to display activity against Gram-negative multidrug-resistant bacteria. In the present work, the influence of hydrophobicity, fluorination, and distribution of cationic/hydrophobic residues on antimicrobial, hemolytic, and cytotoxic properties of α-peptide/β-peptoid hybrids were investigated. An array of 22 peptidomimetics was tested. Analogues with enhanced hydrophobicity were found to exhibit increased activity against Gram-positive bacteria. Incorporation of fluorinated residues into the peptidomimetics conferred increased potency against Gram-positive bacteria, while hemolytic properties and activity against Gram-negative bacteria depended on the degree and type of fluorination. Generally, shorter oligomers were less potent than the corresponding longer analogues. However, some short analogues exhibited equal or higher antimicrobial activity. The alternating hydrophobic/cationic design proved superior to other distribution patterns of cationic side chains and hydrophobic moieties.

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Lysine-Based α-peptide/β-peptoid peptidomimetics: Influence of hydrophobicity, fluorination and distribution of cationic charge on antimicrobial activity and cytotoxicity

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