title: Antimicrobial activity of truncated alpha-defensin (human neutrophil peptide (HNP)-1) analogues without disulphide bridges.
abstract: Antimicrobial peptides play an important role in host defence, particularly in the oral cavity where there is constant challenge by microorganisms. The alpha-defensin antimicrobial peptides comprise 30-50% of the total protein in the azurophilic granules of human neutrophils, the most abundant of which is human neutrophil peptide 1 (HNP-1). Despite its antimicrobial activity, a limiting factor in the potential therapeutic use of HNP-1 is its chemical synthesis with the correct disulphide topology. In the present study, we synthesised a range of truncated defensin analogues lacking disulphide bridges. All the analogues were modelled on the C-terminal region of HNP-1 and their antimicrobial activity was tested against a range of microorganisms, including oral pathogens. Although there was variability in the antimicrobial activity of the truncated analogues synthesised, a truncated peptide named 2Abz(23)S(29) displayed a broad spectrum of antibacterial activity, effectively killing all the bacterial strains tested. The finding that truncated peptides, modelled on the C-terminal beta-hairpin region of HNP-1 but lacking disulphide bridges, display antimicrobial activity could aid their potential use in therapeutic interventions.
authors.affiliation: Oral Science Research Centre, School of Medicine and Dentistry, Queen's University Belfast, Belfast BT12 6BP, Northern Ireland, UK. f.lundy@qub.ac.uk
authors.forename: Fionnuala T
authors.initials: FT
authors.lastname: Lundy
authors.forename: John
authors.initials: J
authors.lastname: Nelson
authors.forename: Derek
authors.initials: D
authors.lastname: Lockhart
authors.forename: Brett
authors.initials: B
authors.lastname: Greer
authors.forename: Pat
authors.initials: P
authors.lastname: Harriott
authors.forename: John J
authors.initials: JJ
authors.lastname: Marley
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004220:Disulfides / Q000378:metabolism*; D006801:Humans; D007526:Isoelectric Point; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000494:pharmacology*; D023084:alpha-Defensins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004220:Disulfides; D050505:Mutant Proteins; D023084:alpha-Defensins; C406413:human neutrophil peptide 1