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Characterization of the branched antimicrobial peptide M6 by analyzing its mechanism of action and in vivo toxicity
Author(s) -
Pini Alessandro,
Giuliani Andrea,
Falciani Chiara,
Fabbrini Monica,
Pileri Silvia,
Lelli Barbara,
Bracci Luisa
Publication year - 2007
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.858
Subject(s) - in vivo , peptide , antimicrobial , antimicrobial peptides , toxicity , mechanism of action , chemistry , lipopolysaccharide , in vitro , cathelicidin , immune system , biochemistry , biology , pharmacology , microbiology and biotechnology , immunology , genetics , organic chemistry
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. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.