Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.662401
Title: Dynamic peptide libraries
Author: Stefanowicz, Fiona Alison
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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Abstract:
The protease thermolysin has been used directly to synthesise dipeptides from Fmoc-protected amino acids on a PEGA1900 solid support. The thermolysin-catalysed solid phase synthesis of longer peptides is reported. Fmoc-protected peptides as long as hexamers (poly-L-leucine) and tetramers (poly-L-phenylalanine and poly-L-tyrosine) were enzymatically synthesised. In each case enzymatic synthesis of peptides resulted in the formation of a library of peptides varying in length, the formation of which was caused by “scrambling” by the enzyme. Due to the reversible nature of the enzyme catalysed peptide bonds, it was believed that the aforementioned solid phase peptide libraries may be exploited to generate dynamic peptide libraries. From the Juliá-Colonna asymmetric epoxidation it is known that chalcone undergoes non-covalent interactions with the amino terminus of poly-L-leucine. Chalcone was therefore employed as a suitable template for the PEGA1900 immobilised poly-L-leucine libraries. However, it was found that the Fmoc-protecting group used in these libraries inhibited binding of chalcone to poly-L-leucine. As an alternative, unprotected poly-L-leucine libraries were generated in solution phase from dileucine using thermolysin. The catalytic activity of poly-L-leucine library members and poly-L-phenylalanine library members in the Juliá-Colonna epoxidation was investigated.  These investigations demonstrated that the peptide amplified by chalcone in the dynamic combinatorial libraries displayed an improved catalytic activity in comparison to other library members. This indicates that dynamic peptide libraries may be exploited as a tool for identifying potential catalysts for the Juliá-Colonna asymmetric epoxidation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.662401  DOI: Not available
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