Synthetic analogs of anoplin show improved antimicrobial activities

Jens Munk; Lars Erik Uggerhøj; Tanja Juul Poulsen; Niels Frimodt-Møller; Reinhard Wimmer; Niels T. Nyberg; Paul Robert Hansen

doi:10.1002/psc.2548

Synthetic analogs of anoplin show improved antimicrobial activities

Jens Munk, Lars Erik Uggerhøj, Tanja Juul Poulsen, Niels Frimodt-Møller, Reinhard Wimmer, Niels T. Nyberg, Paul Robert Hansen

29 Citations (Scopus)

Abstract

We present the antimicrobial and hemolytic activities of the decapeptide anoplin and 19 analogs thereof tested against methicillin-resistant Staphylococcus aureus ATCC 33591 (MRSA), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), vancomycin-resistant Enterococcus faecium (ATCC 700221) (VRE), and Candida albicans (ATCC 200955). The anoplin analogs contain substitutions in amino acid positions 2, 3, 5, 6, 8, 9, and 10. We use these peptides to study the effect of altering the charge and hydrophobicity of anoplin on activity against red blood cells and microorganisms. We find that increasing the charge and/or hydrophobicity improves antimicrobial activity and increases hemolytic activity. For each strain tested, we identify at least six anoplin analogs with an improved therapeutic index compared with anoplin, the only exception being Enterococcus faecium, against which only few compounds are more specific than anoplin. Both 2Nal⁶ and Cha⁶ show improved therapeutic index against all strains tested.

Original language	English
Journal	Journal of Peptide Science
Volume	19
Issue number	11
Pages (from-to)	669-75
ISSN	1075-2617
DOIs	https://doi.org/10.1002/psc.2548
Publication status	Published - Nov 2013

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title = "Synthetic analogs of anoplin show improved antimicrobial activities",

abstract = "We present the antimicrobial and hemolytic activities of the decapeptide anoplin and 19 analogs thereof tested against methicillin-resistant Staphylococcus aureus ATCC 33591 (MRSA), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), vancomycin-resistant Enterococcus faecium (ATCC 700221) (VRE), and Candida albicans (ATCC 200955). The anoplin analogs contain substitutions in amino acid positions 2, 3, 5, 6, 8, 9, and 10. We use these peptides to study the effect of altering the charge and hydrophobicity of anoplin on activity against red blood cells and microorganisms. We find that increasing the charge and/or hydrophobicity improves antimicrobial activity and increases hemolytic activity. For each strain tested, we identify at least six anoplin analogs with an improved therapeutic index compared with anoplin, the only exception being Enterococcus faecium, against which only few compounds are more specific than anoplin. Both 2Nal6 and Cha6 show improved therapeutic index against all strains tested.",

author = "Jens Munk and Uggerh{\o}j, {Lars Erik} and Poulsen, {Tanja Juul} and Niels Frimodt-M{\o}ller and Reinhard Wimmer and Nyberg, {Niels T.} and Hansen, {Paul Robert}",

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TY - JOUR

T1 - Synthetic analogs of anoplin show improved antimicrobial activities

AU - Munk, Jens

AU - Uggerhøj, Lars Erik

AU - Poulsen, Tanja Juul

AU - Frimodt-Møller, Niels

AU - Wimmer, Reinhard

AU - Nyberg, Niels T.

AU - Hansen, Paul Robert

PY - 2013/11

Y1 - 2013/11

N2 - We present the antimicrobial and hemolytic activities of the decapeptide anoplin and 19 analogs thereof tested against methicillin-resistant Staphylococcus aureus ATCC 33591 (MRSA), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), vancomycin-resistant Enterococcus faecium (ATCC 700221) (VRE), and Candida albicans (ATCC 200955). The anoplin analogs contain substitutions in amino acid positions 2, 3, 5, 6, 8, 9, and 10. We use these peptides to study the effect of altering the charge and hydrophobicity of anoplin on activity against red blood cells and microorganisms. We find that increasing the charge and/or hydrophobicity improves antimicrobial activity and increases hemolytic activity. For each strain tested, we identify at least six anoplin analogs with an improved therapeutic index compared with anoplin, the only exception being Enterococcus faecium, against which only few compounds are more specific than anoplin. Both 2Nal6 and Cha6 show improved therapeutic index against all strains tested.

AB - We present the antimicrobial and hemolytic activities of the decapeptide anoplin and 19 analogs thereof tested against methicillin-resistant Staphylococcus aureus ATCC 33591 (MRSA), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), vancomycin-resistant Enterococcus faecium (ATCC 700221) (VRE), and Candida albicans (ATCC 200955). The anoplin analogs contain substitutions in amino acid positions 2, 3, 5, 6, 8, 9, and 10. We use these peptides to study the effect of altering the charge and hydrophobicity of anoplin on activity against red blood cells and microorganisms. We find that increasing the charge and/or hydrophobicity improves antimicrobial activity and increases hemolytic activity. For each strain tested, we identify at least six anoplin analogs with an improved therapeutic index compared with anoplin, the only exception being Enterococcus faecium, against which only few compounds are more specific than anoplin. Both 2Nal6 and Cha6 show improved therapeutic index against all strains tested.

U2 - 10.1002/psc.2548

DO - 10.1002/psc.2548

M3 - Journal article

SN - 1075-2617

VL - 19

SP - 669

EP - 675

JO - Journal of Peptide Science

JF - Journal of Peptide Science

IS - 11

ER -

Synthetic analogs of anoplin show improved antimicrobial activities

Abstract

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