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.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK, 2100, Copenhagen Ø, Denmark.
authors.forename: Jens K
authors.initials: JK
authors.lastname: Munk
authors.forename: Lars Erik
authors.initials: LE
authors.lastname: Uggerhøj
authors.forename: Tanja J
authors.initials: TJ
authors.lastname: Poulsen
authors.forename: Niels
authors.initials: N
authors.lastname: Frimodt-Møller
authors.forename: Reinhard
authors.initials: R
authors.lastname: Wimmer
authors.forename: Nils T
authors.initials: NT
authors.lastname: Nyberg
authors.forename: Paul R
authors.initials: PR
authors.lastname: Hansen
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D016984:Enterococcus faecium / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D053878:Hemolytic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D014862:Wasp Venoms / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D053878:Hemolytic Agents; D014862:Wasp Venoms; C443041:anoplin
keywords: anoplin; antimicrobial peptide; antimicrobial resistance; antimicrobials; therapeutic index