Tailoring Cytotoxicity of Antimicrobial Peptidomimetics with High Activity against Multidrug-Resistant Escherichia coli

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Tailoring Cytotoxicity of Antimicrobial Peptidomimetics with High Activity against Multidrug-Resistant Escherichia coli. / Jahnsen, Rasmus D; Sandberg-Schaal, Anne; Vissing, Karina Juul; Nielsen, Hanne Mørck; Frimodt-Møller, Niels; Franzyk, Henrik.

I: Journal of Medicinal Chemistry, Bind 57, Nr. 7, 20.03.2014, s. 2864-2873.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Jahnsen, RD, Sandberg-Schaal, A, Vissing, KJ, Nielsen, HM, Frimodt-Møller, N & Franzyk, H 2014, 'Tailoring Cytotoxicity of Antimicrobial Peptidomimetics with High Activity against Multidrug-Resistant Escherichia coli', Journal of Medicinal Chemistry, bind 57, nr. 7, s. 2864-2873. https://doi.org/10.1021/jm401335p

APA

Jahnsen, R. D., Sandberg-Schaal, A., Vissing, K. J., Nielsen, H. M., Frimodt-Møller, N., & Franzyk, H. (2014). Tailoring Cytotoxicity of Antimicrobial Peptidomimetics with High Activity against Multidrug-Resistant Escherichia coli. Journal of Medicinal Chemistry, 57(7), 2864-2873. https://doi.org/10.1021/jm401335p

Vancouver

Jahnsen RD, Sandberg-Schaal A, Vissing KJ, Nielsen HM, Frimodt-Møller N, Franzyk H. Tailoring Cytotoxicity of Antimicrobial Peptidomimetics with High Activity against Multidrug-Resistant Escherichia coli. Journal of Medicinal Chemistry. 2014 mar 20;57(7):2864-2873. https://doi.org/10.1021/jm401335p

Author

Jahnsen, Rasmus D ; Sandberg-Schaal, Anne ; Vissing, Karina Juul ; Nielsen, Hanne Mørck ; Frimodt-Møller, Niels ; Franzyk, Henrik. / Tailoring Cytotoxicity of Antimicrobial Peptidomimetics with High Activity against Multidrug-Resistant Escherichia coli. I: Journal of Medicinal Chemistry. 2014 ; Bind 57, Nr. 7. s. 2864-2873.

Bibtex

@article{175be2dbfb224da9a627cfef1094a175,
title = "Tailoring Cytotoxicity of Antimicrobial Peptidomimetics with High Activity against Multidrug-Resistant Escherichia coli",
abstract = "Infections with multidrug-resistant pathogens are an increasing concern for public health. Recently, subtypes of peptide-peptoid hybrids were demonstrated to display potent activity against multidrug-resistant Gram-negative bacteria. Here, structural variation of these antibacterial peptidomimetics was investigated as a tool for optimizing cell selectivity. A protocol based on dimeric building blocks allowed for efficient synthesis of an array of peptide-peptoid oligomers representing length variation as well as different backbone designs displaying chiral or achiral peptoid residues. Lack of α-chirality in the side chains of the peptoid residues proved to be correlated to reduced cytotoxicity. Furthermore, optimization of the length of these peptidomimetics with an alternating cationic-hydrophobic design was a powerful tool to enhance the selectivity against Gram-negative pathogens over benign mammalian cells. Thus, lead compounds with a high selectivity toward killing of clinically important multidrug-resistant E. coli were identified.",
author = "Jahnsen, {Rasmus D} and Anne Sandberg-Schaal and Vissing, {Karina Juul} and Nielsen, {Hanne M{\o}rck} and Niels Frimodt-M{\o}ller and Henrik Franzyk",
year = "2014",
month = mar,
day = "20",
doi = "10.1021/jm401335p",
language = "English",
volume = "57",
pages = "2864--2873",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "7",

}

RIS

TY - JOUR

T1 - Tailoring Cytotoxicity of Antimicrobial Peptidomimetics with High Activity against Multidrug-Resistant Escherichia coli

AU - Jahnsen, Rasmus D

AU - Sandberg-Schaal, Anne

AU - Vissing, Karina Juul

AU - Nielsen, Hanne Mørck

AU - Frimodt-Møller, Niels

AU - Franzyk, Henrik

PY - 2014/3/20

Y1 - 2014/3/20

N2 - Infections with multidrug-resistant pathogens are an increasing concern for public health. Recently, subtypes of peptide-peptoid hybrids were demonstrated to display potent activity against multidrug-resistant Gram-negative bacteria. Here, structural variation of these antibacterial peptidomimetics was investigated as a tool for optimizing cell selectivity. A protocol based on dimeric building blocks allowed for efficient synthesis of an array of peptide-peptoid oligomers representing length variation as well as different backbone designs displaying chiral or achiral peptoid residues. Lack of α-chirality in the side chains of the peptoid residues proved to be correlated to reduced cytotoxicity. Furthermore, optimization of the length of these peptidomimetics with an alternating cationic-hydrophobic design was a powerful tool to enhance the selectivity against Gram-negative pathogens over benign mammalian cells. Thus, lead compounds with a high selectivity toward killing of clinically important multidrug-resistant E. coli were identified.

AB - Infections with multidrug-resistant pathogens are an increasing concern for public health. Recently, subtypes of peptide-peptoid hybrids were demonstrated to display potent activity against multidrug-resistant Gram-negative bacteria. Here, structural variation of these antibacterial peptidomimetics was investigated as a tool for optimizing cell selectivity. A protocol based on dimeric building blocks allowed for efficient synthesis of an array of peptide-peptoid oligomers representing length variation as well as different backbone designs displaying chiral or achiral peptoid residues. Lack of α-chirality in the side chains of the peptoid residues proved to be correlated to reduced cytotoxicity. Furthermore, optimization of the length of these peptidomimetics with an alternating cationic-hydrophobic design was a powerful tool to enhance the selectivity against Gram-negative pathogens over benign mammalian cells. Thus, lead compounds with a high selectivity toward killing of clinically important multidrug-resistant E. coli were identified.

U2 - 10.1021/jm401335p

DO - 10.1021/jm401335p

M3 - Journal article

C2 - 24601601

VL - 57

SP - 2864

EP - 2873

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 7

ER -

ID: 104938985