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Title: New tools for target identification by affinity chromatography
Author: Landi, Felicetta
ISNI:       0000 0004 2730 2949
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2011
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The recovery of the selected biological material in affinity-based separations relies on reversing the biological interaction responsible for the binding. General elution methods which are independent of the bioaffinity interaction have attracted increasing attention. The first three chapters of this thesis describe the development of a novel “click” functionalised azobenzene-based linker for affinity-independent elution protocols and the preliminary affinity studies using this linker. Ligands functionalised with a bioorthogonal propargyl label were readily attached to the terminal azide of the linker using the copper(I) catalysed Huisgen cycloaddition (or "click" reaction). Following separation, the linker was cleaved under mild non-denaturing conditions using Na2S2O4. In the last three chapters a novel approach towards the synthesis of the 4-methyl proline fragment of the cytotoxic natural product bisebromoamide (a potential affinity target) is proposed. For the pyrrolidine ring construction an enamide-olefin ring-closing metathesis (RCM) approach has been attempted. The installation of the required absolute stereochemistry has been achieved using a phase-transfer catalyst for the enantioselective alkylation of Schiff bases derived from glycine esters.
Supervisor: Hulme, Alison N. ; Bradley, Mark. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: affinity-based separations ; bioaffinity interaction ; click ; bioorthogonal propargyl