Synthetic analogs of anoplin show improved antimicrobial activities

Jens Kristian Munk, Lars Erik Uggerhøj, Tanja J. Poulsen, Niels Frimodt-Møller, Reinhard Wimmer, Nils T. Nyberg, Paul R. Hansen

Research output: Contribution to journalJournal articleResearchpeer-review

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. © 2013 European Peptide Society and John Wiley & Sons, Ltd.
Original languageEnglish
JournalJournal of Peptide Science
Volume19
Issue number11
Pages (from-to)669-675
ISSN1075-2617
DOIs
Publication statusPublished - 2013
Externally publishedYes

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

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