Synthetic analogs of anoplin show improved antimicrobial activities

• Published in: Journal of peptide science Vol. 19; no. 11; pp. 669 - 675
• Main Authors: Munk, Jens K., Uggerhøj, Lars Erik, Poulsen, Tanja J., Frimodt-Møller, Niels, Wimmer, Reinhard, Nyberg, Nils T., Hansen, Paul R.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2013; Wiley Subscription Services, Inc
• Subjects: Amino acid substitution; anoplin; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Antifungal Agents - chemical synthesis; Antifungal Agents - pharmacology; Antimicrobial Cationic Peptides - chemical synthesis; Antimicrobial Cationic Peptides - pharmacology; antimicrobial peptide; antimicrobial resistance; antimicrobials; Candida albicans; Candida albicans - drug effects; Drug Resistance, Bacterial; Enterococcus faecium - drug effects; Erythrocytes - drug effects; Escherichia coli - drug effects; Hemolytic Agents - chemical synthesis; Hemolytic Agents - pharmacology; Humans; Hydrophobic and Hydrophilic Interactions; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Peptides; Pseudomonas aeruginosa - drug effects; therapeutic index; Wasp Venoms - chemical synthesis; Wasp Venoms - pharmacology; anoplin; antimicrobials; antimicrobial peptide; antimicrobial resistance; therapeutic index
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.2548

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. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. Anoplin, GLLKRIKTLL‐NH2, is a decamer amide antimicrobial peptide from wasp venom. We report the effects on hemolytic and bacteriostatic activities of the modifications shown, where X is the cyclohexylalanine of 2‐naphthylalanine.