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|Title: ||Biophysical studies to elucidate structure-activity relationships in β-defensins|
|Authors: ||De Cecco, Martin|
|Supervisor(s): ||Barran, Perdita|
|Issue Date: ||27-Jun-2011|
|Publisher: ||The University of Edinburgh|
|Abstract: ||β-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
|Sponsor(s): ||Engineering and Physical Sciences Research Council (EPSRC)|
|Keywords: ||ion mobility|
|Appears in Collections:||Chemistry thesis and dissertation collection|
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