title: Characterization of the branched antimicrobial peptide M6 by analyzing its mechanism of action and in vivo toxicity.
abstract: We analyzed functional activity of the antimicrobial peptide M6 in vitro and in vivo. The peptide was identified by our group by phage library selection, rational modification and synthesis in a tetrabranched form (Pini et al., Antimicrob. Agents Chemother. 2005; 49: 2665-72). We found that it binds lipopolysaccharide, causes perforation of cell membranes without destroying external cell morphology and strongly binds DNA. The latter feature suggests that it could inhibit metabolic pathways, blocking DNA replication and/or transcription. We also observed that M6 does not stimulate humoral immune response when repeatedly administered to animals. We also analyzed M6 toxicity when administered to animals by intraperitoneal or by intravenous injection, determining a preliminary LD50 (125 and 37.5 mg/kg, respectively), which suggested that M6 could be used in vivo. These features make the antimicrobial branched peptide M6 a promising candidate for the development of a new antibacterial drug.
authors.affiliation: Dipartimento di Biologia molecolare, Università degli Studi di Siena, Via Fiorentina 1, 53100, Siena, Italy. pinia@unisi.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pini
authors.forename: Andrea
authors.initials: A
authors.lastname: Giuliani
authors.forename: Chiara
authors.initials: C
authors.lastname: Falciani
authors.forename: Monica
authors.initials: M
authors.lastname: Fabbrini
authors.forename: Silvia
authors.initials: S
authors.lastname: Pileri
authors.forename: Barbara
authors.initials: B
authors.lastname: Lelli
authors.forename: Luisa
authors.initials: L
authors.lastname: Bracci
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D008070:Lipopolysaccharides / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D020349:Surface Plasmon Resonance
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D010455:Peptides