Analyses of murine beta defensins and defensin inspired peptides

• Main Author: Taylor, Karen
• Published: University of Edinburgh 2007
• Subjects: 572.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.662769

The defensins, one of the largest antimicrobial peptide families, can be subclassed into the α, β and θ defensins based on their six cysteine spacing and connectivity. The β-defensins which are expressed at a variety of epithelial surfaces, display antimicrobial properties and play important roles in host defence. The aim of this project was 1) to evaluate the antimicrobial and chemoattractant properties of a novel five cysteine defensin related peptide (Defr1), 2) to analyse Defb14 (the murine orthologue of human beta defensin 3 and 3) to investigate the properties of defensin inspired peptides. This thesis describes the antimicrobial and chemoattractant properties of Defr1. This work suggests that Defr1 displayed antimicrobial activity against a panel of organisms for which antimicrobial treatment is limited or non-existent. In addition Defr1 displayed potent chemoattractant properties regarding various immune cell types and is the first example of a β-defensin that does not act through CCR6. Data presented in this thesis describes the first study of the murine peptide Defb14. This concluded that a synthetic preparation of Defb14 displayed potent antimicrobial activity and roles within immune cell migration. In this thesis, various defensin inspired peptides were subjected to study. Defb14 was used as a template for functional analysis and concluded that smaller N-terminal peptides displayed potent antimicrobial activity. Interestingly chemotactic activity was absent and toxicity remained similar to that of the original Defb14. These studies have highlighted the role of defensin inspired peptides as potential therapeutic agents.