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Title: Functional studies of novel alpha helical peptides
Author: McLean , Denise Theresa
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2013
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The incidence of antibiotic resistance amongst bacteria has increased steadily due to the over prescription of antibiotics for minor ailments in addition to their overuse in the agricultural industry. As such it is imperative that we identify new therapies to combat the growing threat from antibiotic resistant pathogens. The aim of this study was to investigate the antimicrobial potential of a number of novel alpha helical peptides from diverse sources. These peptides shared common biophysical features of host defense peptides (HDPs) such as size, cationicity and amphipathicity. The nature of these peptides suggests they could function as topical antimicrobial agents and the oral cavity represents an ideal location for their use . This study has shown that truncation of LL-37 to produce shorter mimetics generates peptides with enhanced antimicrobial efficacy against a range of oral pathogens in addition to pathogens from the skin, lung and gut. In one case truncation of LL-37 produced a peptide (KE-18) with increased potential to bind to lipopolysaccharide and lipoteichoic acid. A further mimetic, KR-12 has potent an ti-candidal peptide with decreased haemolytic activity. In addition this study has shown that the truncated mimetics of LL-37 investigated had a similar mechanism of action to that of the parent molecule as all were shown to disrupt the bacterial membrane. Peptides from the African volcano frog (Xenopus amieti) displayed potent antimicrobial efficacy against a range 'of oral pathogens. Then exhibited minimal haemolytic activity suggesting these peptides may be useful templates for the development of possible therapeutics designed for the oral cavity. PGLa-AMl and CPF-AMl both displayed excellent ability to inhibit the growth of Streptococcus mutons suggesting these peptides could have a potential role in the prevention of dental carries. ~. The study identified a number of "cryptic" peptides (the 10 family of peptides) which , displayed antimicrobial activity and some ability to bind to lipopolysaccharide. One peptide (31Q3) merited further investigation as the others showed modest antimicrobial activity against examples of Gram positive, Gram negative and fungal pathogens. Overall, this study has identified a number of alpha helical peptides which have the potential to be investigated further as possible therapeutics for the treatment of a number of oral conditions .
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available