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Title: Synthesis of glycopeptides and novel glycopeptide mimics
Author: Blanc-Melia, Javier
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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A scalable synthesis of core-1 disaccharide (β-galactose(1-3)α-N-acetylgalactosamine), O-linked to threonine was accomplished. This building block was then incorporated into a peptide using solid phase peptide synthesis. Additionally, a novel neo-glycopeptide linkage was created using the Cu(l)-catalysed modification of Huisgen cycloaddition (click chemistry) between glycosyl azides and peptides modified with acetylenes moieties. This linkage can be formed either on solid support or in aqueous solution. Moreover, we investigated the synthesis on solid phase of a tripeptide scaffold (Ac-L-Cys-L-Lys-L-Cys-NH2) that displays the N-acetyllactosamine through the thiol groups of the two cysteine residues as a potential 'oligosaccaride mimic'. This structure can be linked to a peptide via the glycosyl azide of N-acetylglucosamine appended to the amino group of the central lysine residue. Therefore, two such oligosaccharide mimics were incorporated into an erythropoietin (EPO) derived peptide fragment of 69% yield using our novel neo-glycopeptide linkage in a buffered solution. To demonstrate the tripeptide scaffold displays carbohydrates correctly, and be recognised in a biological environment, the EPO peptide fragment bearing two oligosaccharide mimics was joined to a Green Fluorescent Protein C-terminal thioester using native chemical ligation. Afterwards, the protein-carbohydrate interaction was observed between this glycoprotein mimetic and lectin Ricinnus communis RCA120 immobilised on agarose beads.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available