Antimicrobial activity of truncated alpha-defensin (human neutrophil peptide (HNP)-1) analogues without disulphide bridges.

Fionnuala Lundy, John Nelson, D. Lockhart, Brett Greer, Patrick Harriott, John Marley

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Antimicrobial peptides play an important role in host defence, particularly in the oral cavity where there is constant challenge by microorganisms. The a-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 2Abz23S29 displayed a broad spectrum of antibacterial activity, effectively killing all the bacterial strains tested. The finding that truncated peptides, modelled on the C-terminal ß-hairpin region of HNP-1 but lacking disulphide bridges, display antimicrobial activity could aid their potential use in therapeutic interventions.
Original languageEnglish
Pages (from-to)190-193
Number of pages4
JournalMolecular Immunology
Volume45
Issue number1
DOIs
Publication statusPublished - Jan 2008

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alpha-Defensins
Disulfides
Defensins
Peptides
Therapeutic Uses
Mouth
Neutrophils
human neutrophil peptide 1
Proteins

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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 a-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 2Abz23S29 displayed a broad spectrum of antibacterial activity, effectively killing all the bacterial strains tested. The finding that truncated peptides, modelled on the C-terminal {\ss}-hairpin region of HNP-1 but lacking disulphide bridges, display antimicrobial activity could aid their potential use in therapeutic interventions.",
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Antimicrobial activity of truncated alpha-defensin (human neutrophil peptide (HNP)-1) analogues without disulphide bridges. / Lundy, Fionnuala; Nelson, John; Lockhart, D.; Greer, Brett; Harriott, Patrick; Marley, John.

In: Molecular Immunology, Vol. 45 , No. 1, 01.2008, p. 190-193.

Research output: Contribution to journalArticle

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