Approach to a synthetic esterase
Morris, David J. (2001) Approach to a synthetic esterase. PhD thesis, University of Warwick.
WRAP_THESIS_Morris_2001.pdf - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Official URL: http://webcat.warwick.ac.uk/record=b1372170~S15
Project A: The development of a supported sixteen residue peptidyl model incorporating the 'reactive triad' serine, histidine and aspartic acid, found within serine protease enzymes. The methodology was designed to allow rapid screening of a combinatorial library of simple peptides containing the reactive triad, some of which were anticipated to show synthetic esterase activity. It is envisaged that this could be undertaken be observing selective cleavage of a highly coloured red azo dye tethered through the ester under investigation to the peptide via a glycol linker. One peptidyl system has been synthesised and investigated to allow the development of the methodology and it was found that intramolecular hydrolysis could be observed when glycol linkers of optimal length were utilised under favourable conditions.
Project B: Vancomycin was modified with extended glycol chains containing a terminal double bond to allow covalent dimerisation via cross coupling metathesis. Binding of the vancomycin monomers and dimers to an N-acetyl-L-Lys-D-Ala-D-Ser peptide model has been demonstrated via electrospray ionisation mass spectrometry by Professor Albert Heck at Utrecht, Holland and in-vivo studies are ongoing to elucidate if enhanced vancomycin activity towards vancomycin resistant bacteria can be observed.
|Item Type:||Thesis or Dissertation (PhD)|
|Subjects:||Q Science > QP Physiology|
|Library of Congress Subject Headings (LCSH):||Esterases -- Research, Enzymes -- Synthesis, Peptides -- Synthesis, Vancomycin -- Research|
|Official Date:||January 2001|
|Institution:||University of Warwick|
|Theses Department:||Department of Chemistry|
|Format of File:|
|Extent:||242 leaves : col. ill., charts|
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