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Title: Design and synthesis of peptides derived from nucleoside β-amino acids
Author: Turtle, Michelle Louise
ISNI:       0000 0004 2734 1542
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2012
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Naturally occurring macromolecules such as proteins and DNA adopt very specific conformations and three dimensional arrangements which allow them to perform their sophisticated functions in nature. Unnatural oligomerscan also adopt well defined conformations and these have been termed 'foldamers'. This project is concerned with the design and synthesis of β-peptide foldamers which are assembled from nucleoside derived β -amino acids. It was hoped that the combination of the inherent helix folding properties of peptides and the associated characteristics of nucleosides would allow us to create novel foldamers with specific recognition properties. The structure of the β -amino acids involves conversion of the 3'-hydroxyl group of the nucleoside sugar into an amino group (with retention of configuration) and oxidation of the 5'-hydroxymethylene group to a carboxylic acid. Beginning with the natural nucleosides thymidine and 2'-deoxyadenosine, syntheses of 4 different nucleoside β -amino acid monomers was accomplished. The syntheses were based around the use of 3'-azido-2'-deoxynucleosides as key synthetic intermediates and also required optimisation of protecting groups to prevent side reactions associated with cleavage of the glycosidic bond. In general, the preferred protecting group strategy involved the 3'-amino group being either protected with a fluorenylmethoxycarbonyl (Fmoc) group or being masked as an azide. The benzhydryl group also proved useful in the protection of the carboxylic acid function for couplings in solution. The synthesis of the β -peptides was investigated by both solid-phase peptide synthesis and standard couplings in solution. A range of peptide dimers, trimers and a tetramer were prepared, but the isolated yields of the final products were low due to difficulties with purification.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral