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dc.contributor.advisorBarran, Perdita
dc.contributor.authorDe Cecco, Martin
dc.contributor.authorCampopiano, Dominic
dc.date.accessioned2011-06-28T14:56:26Z
dc.date.available2011-06-28T14:56:26Z
dc.date.issued2011-06-27
dc.identifier.urihttp://hdl.handle.net/1842/4931
dc.description.abstractβ-defensins are a class of mammalian defence peptides with therapeutic potential because of their ability to kill bacteria and attract host immune cells. In order to realise this potential, it is necessary to understand how the functions of these peptides are related to their structures. This thesis presents biophysical analysis of β- defensins and related peptides in conjunction with biological assays. These studies provide new insights into the structure-activity relationships of β-defensins. Ion mobility-mass spectrometry (IM-MS) is used throughout this thesis to probe the tertiary structure of peptides in vacuo and, by inference, make conclusions about their conformations in solution prior to ionisation. Where appropriate, IM-MS is complemented by other techniques, including high performance liquid chromatography and circular dichroism spectroscopy. First, the importance of a C-terminal cysteine residue within the murine β-defensin Defb14 is investigated. The functional and structural implications of chemically modifying the cysteine residue are examined. Second, the N-terminal region of Defb14 is modified by the substitution and deletion of amino acids. Again, the effects on biological activity and structure are discussed. Finally, the functional and structural overlap of β-defensins with another family of proteins – the chemokines – is considered. The oligomerisation of β-defensins and their interaction with glycosaminoglycans is of particular interest: structural data for human β-defensins 2 and 3 in the absence and presence of polysaccharides are presented.en
dc.contributor.sponsorEngineering and Physical Sciences Research Council (EPSRC)en
dc.language.isoenen
dc.publisherThe University of Edinburghen
dc.relation.hasversion‘Conformational preferences of linear β-defensins are revealed by ion mobility-mass spectrometry’ M. De Cecco, E. S. Seo, D. J. Clarke, B. J. McCullough, K. Taylor, D Macmillan, J. R. Dorin, D. J. Campopiano and P. E. Barran, J. Phys. Chem. B, 2010, 114, 2312.en
dc.relation.hasversionIsoleucine/leucine-2 is essential for chemoattractant activity of β-defensin Defb14 through chemokine receptor 6’ C. Tyrrell, M. De Cecco, N. L. Reynolds, F. Kilanowski, D. Campopiano, P. Barran, D. Macmillan and J. R. Dorin, Mol. Immunol., 2010, 47, 1378.en
dc.relation.hasversion‘Peptide fragments of a β-defensin derivative with potent bactericidal activity’ N. L. Reynolds, M. De Cecco, K. Taylor, C. Stanton, F. Kilanowski, J. Kalapothakis, E. Seo, D. Uhrin, D. Campopiano, J. Govan, D. Macmillan, P. Barran and J. R. Dorin, Antimicrob. Agents Chemother., 2010, 54, 1922.en
dc.relation.hasversion‘Interaction of human β-defensin 2 (HBD2) with glycosaminoglycans’ E. S. Seo, B. S. Blaum, T. Vargues, M. De Cecco, J. A. Deakin, M. Lyon, P. E. Barran, D. J. Campopiano and D. Uhrin, Biochemistry, 2010, 49, 10486.en
dc.subjection mobilityen
dc.subjectmass spectrometryen
dc.subjectdefensinsen
dc.subjectpeptidesen
dc.titleBiophysical studies to elucidate structure-activity relationships in β-defensinsen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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