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Title: Studies on peptides and peptide mimetics
Author: Howells, A.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 1998
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Part 1: Development of a racemisation free process of attaching the first amino acid to a solid resin support for peptide synthesis. To overcome the high degree of racemisation of the amino acid in this process, we have explored a new kind of method of attaching this first amino acid to a resin. This approach involves activating the alcohol of the polyamide resin, instead of activating the amino acid. To test this theory we used benzyl alcohol as a model for the resin, and activated the alcohol with diisopropylcarbodiimide to form an O-isourea derivative. A detailed kinetic study was carried out to establish the rate of reaction with different benzyl alcohols, which proved that solution phase formation of the benzyl esters was successful. We were unable to attach the first amino acid to the resin support, which we believe is due to the reagents being unable to interact with the alcohol sites which are inside the bead of the resin. Part 2: Development of a novel peptidomimetic constraint. Current interest in the development of β-turn stabilising constraints for biologically active peptide motifs led us to synthesise a novel peptidomimetic molecule which in its cis form would provide a scaffold to constrain the conformation of a linear peptide. In stereochemically pure form the BocNH and CO2Et would be pointing in the right direction to mimic a β-bend, and could be a prototype for peptidomimetics based on e.g. cell adhesion and anti-aggregatory peptides. The synthesis proved demanding as this dioxopiperazine combines an α-diamino with a β-keto ester system, and although all linear precursors were satisfactorily synthesised, the final step which involved a cyclisation reaction did not work. To remove the complication of a β-keto ester system we then attempted to synthesise (36). (Fig. 3754) Again the pre-cyclisation stages were achieved satisfactorily to yield Z-NHCH(NHBoc)CONHCH(CH2OH)CO2CH3
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available