title: Synthesis and biological activity of lipophilic analogs of the cationic antimicrobial active peptide anoplin.
abstract: Anoplin is a short natural cationic antimicrobial peptide which is derived from the venom sac of the solitary wasp, Anoplius samariensis. Due to its short sequence G1LLKR5IKT8LL-NH2, it is ideal for research tests. In this study, novel analogs of anoplin were prepared and examined for their antimicrobial, hemolytic activity, and proteolytic stability. Specific substitutions were introduced in amino acids Gly1, Arg5, and Thr8and lipophilic groups with different lengths in the N-terminus in order to investigate how these modifications affect their antimicrobial activity. These cationic analogs exhibited higher antimicrobial activity than the native peptide; they are also nontoxic at their minimum inhibitory concentration (MIC) values and resistant to enzymatic degradation. The substituted peptide GLLKF5IKK8LL-NH2exhibited high activity against Gram-negative bacterium Zymomonas mobilis (MIC = 7 µg/ml), and the insertion of octanoic, decanoic, and dodecanoic acid residues in its N-terminus increased the antimicrobial activity against Gram-positive and Gram-negative bacteria (MIC = 5 µg/ml). The conformational characteristics of the peptide analogs were studied by circular dichroism. Structure activity studies revealed that the substitution of specific amino acids and the incorporation of lipophilic groups enhanced the amphipathic α-helical conformation inducing better antimicrobial effects. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece.
authors.forename: Kostas
authors.initials: K
authors.lastname: Chionis
authors.affiliation: Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Krikorian
authors.affiliation: Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece.
authors.forename: Anna-Irini
authors.initials: AI
authors.lastname: Koukkou
authors.affiliation: Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Sakarellos-Daitsiotis
authors.affiliation: Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Panou-Pomonis
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D002175:Candida / Q000187:drug effects / Q000254:growth & development; D004912:Erythrocytes / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019476:Insect Proteins / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D055550:Protein Stability; D017433:Protein Structure, Secondary; D059748:Proteolysis; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013329:Structure-Activity Relationship; D014862:Wasp Venoms / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D014863:Wasps / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D019476:Insect Proteins; D014862:Wasp Venoms; C443041:anoplin
keywords: amphipathic α-helical peptides; anoplin analogs; antimicrobial activity; circular dichroism; hemolytic assay; proteolytic assay