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Title: Synthetic lectins with pyrene at the core
Author: Carter, Tom Scott
ISNI:       0000 0004 6057 8437
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2016
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Carbohydrates are displayed on the outer layer of cells by glycoproteins and glycolipids, forming the glycocalyx. These carbohydrates hold a huge amount of information, acting as a cell 'barcode', facilitating communication and acting as targets for pathogens. The proteins which recognise carbohydrates in nature are called lectins. Synthetic mimics of these proteins, binding through noncovalent interactions in water, are termed 'synthetic lectins'. The design and synthesis of these synthetic lectins could allow reading of parts of the cell barcode and give a greater understanding of the operation of natural lectins. Furthermore, robust selective synthetic lectins could act as sensors for important sugars such as N-acetylglucosamine (important in protein regulation) or blood glucose levels (for surgery or diabetics). However the design of synthetic lectins that are able to overcome the hydromimetic nature of carbohydrates and show selectivity between carbohydrates is very difficult. Within this body of work a variety of synthetic lectin architectures are presented, with their design, synthesis and binding properties reported. Two designs within are of particular note. Firstly, a highly cationic pyrene based platform shaped receptor (PyPlat-Guan) was prepared to target α-sialosides (components of important antigens such as Sialyl Lewis X). This resulted in strong selective binding of methyla α-sialoside and both the first non-macrocyclic synthetic lectin and the first synthetic lectin with divalency by design. Secondly, a pyrene based four-pillared cage receptor was prepared (Py4P) to target O-linked N-acetylglucosamine (O-GlcNAc). This resulted in a pair of receptor isomers, which demonstrate the highest binding affinities ever obtained by a synthetic lectin for a monosaccharide. It was then also possible to test the interaction of these synthetic lectins with a glycopeptide, which was bound with unprecedented affinity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available