Synthetic analogs of anoplin show improved antimicrobial activities

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

Klinisk Mikrobiologisk Afdeling

36 Citationer (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 2Nal(6) and Cha(6) show improved therapeutic index against all strains tested.

Originalsprog	Engelsk
Tidsskrift	Journal of peptide science : an official publication of the European Peptide Society
Vol/bind	19
Udgave nummer	11
Sider (fra-til)	669-675
Antal sider	7
DOI	https://doi.org/10.1002/psc.2548
Status	Udgivet - 2013

Emneord

Anti-Bacterial Agents, Antifungal Agents, Antimicrobial Cationic Peptides, Candida albicans, Drug Resistance, Bacterial, Enterococcus faecium, Erythrocytes, Escherichia coli, Hemolytic Agents, Humans, Hydrophobic and Hydrophilic Interactions, Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, Pseudomonas aeruginosa, Wasp Venoms, anoplin, 2 naphthylalanine, amino acid, anoplin derivative, antiinfective agent, cyclohexylalanine, gentamicin, hemolytic agent, unclassified drug, antimicrobial activity, article, controlled study, drug structure, drug synthesis, erythrocyte, hemolysis, human, hydrophobicity, methicillin resistant Staphylococcus aureus, minimum inhibitory concentration, priority journal, vancomycin resistant Enterococcus, Anoplin, Antimicrobial peptide, Antimicrobial resistance, Antimicrobials, Therapeutic index, antimicrobial peptide, antimicrobials, therapeutic index, antimicrobial resistance

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10.1002/psc.2548

Citationsformater

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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 2Nal(6) and Cha(6) show improved therapeutic index against all strains tested.",

keywords = "Anti-Bacterial Agents, Antifungal Agents, Antimicrobial Cationic Peptides, Candida albicans, Drug Resistance, Bacterial, Enterococcus faecium, Erythrocytes, Escherichia coli, Hemolytic Agents, Humans, Hydrophobic and Hydrophilic Interactions, Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, Pseudomonas aeruginosa, Wasp Venoms, anoplin, 2 naphthylalanine, amino acid, anoplin derivative, antiinfective agent, cyclohexylalanine, gentamicin, hemolytic agent, unclassified drug, antimicrobial activity, article, controlled study, drug structure, drug synthesis, erythrocyte, hemolysis, human, hydrophobicity, methicillin resistant Staphylococcus aureus, minimum inhibitory concentration, priority journal, vancomycin resistant Enterococcus, Anoplin, Antimicrobial peptide, Antimicrobial resistance, Antimicrobials, Therapeutic index, antimicrobial peptide, antimicrobials, therapeutic index, antimicrobial resistance",

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

note = "Copyright {\textcopyright} 2013 European Peptide Society and John Wiley & Sons, Ltd.",

year = "2013",

doi = "10.1002/psc.2548",

language = "English",

volume = "19",

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journal = "Journal of peptide science : an official publication of the European Peptide Society",

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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, Nils

AU - Hansen, Paul Robert

PY - 2013

Y1 - 2013

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 2Nal(6) and Cha(6) 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 2Nal(6) and Cha(6) show improved therapeutic index against all strains tested.

KW - Anti-Bacterial Agents, Antifungal Agents, Antimicrobial Cationic Peptides, Candida albicans, Drug Resistance, Bacterial, Enterococcus faecium, Erythrocytes, Escherichia coli, Hemolytic Agents, Humans, Hydrophobic and Hydrophilic Interactions, Methicillin-

U2 - 10.1002/psc.2548

DO - 10.1002/psc.2548

M3 - Journal article

C2 - 24019229

SN - 1099-1387

SN - 1615-9314

VL - 19

SP - 669

EP - 675

JO - Journal of peptide science : an official publication of the European Peptide Society

JF - Journal of peptide science : an official publication of the European Peptide Society

IS - 11

ER -

Synthetic analogs of anoplin show improved antimicrobial activities

Abstract

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