The overwhelming occurrence and structural diversity of carbohydrates in Nature indicate their importance in a range of fundamental life processes. Indeed, it is this diversity that has lead to the two equally diverse groups of carbohydrate-processing enzymes, namely the glycoside hydrolases and glycosyl transferases. Thus, understanding the role of both carbohydrates and their processing enzymes in biological systems has attracted significant attention. This thesis, firstly, describes endeavours towards the synthesis of an inositol ?- amino acid, along with a series of sugar α-substituted carboxylic acid esters, utilising an extension of the modified Corey-Link reaction. The emphasis of the thesis is then shifted towards the synthesis of a putative inhibitor of a family GH26 lichenase from Clostridium thermocellum (CtLic26A). The preparation of 2-deoxy-2-fluoro-β-laminarbiosyl fluoride 1 is described, along with elaboration into oligosaccharides utilising AbgE358G glycosynthase technology. Crystallographic investigations indicated that the transition state adopted by CtLic26A is in stark contrast to that utilised by the related family GH26 mannanase from Pseudomonas cellulose (Man26A). ... Following on from this work, expanding the role of the AbgE358G glycosynthase acceptor repertoire to accommodate inositol substrates was explored, furthering the synthetic utility of this enzyme. Thus, a number of inositol acceptors bearing an aryl anchor, for example 2, were prepared and shown to be surrogates for carbohydrate acceptors. ... The thesis then describes the synthesis of an acetamide derivative of 1-epivalienamine, namely 3, a putative inhibitor of β-N-acetylglucosaminidases. Both the synthesis of 3, along with kinetic data for four β-N-acetylglucosaminidases, is reported; as well, Western blot analysis indicated no inhibition of a recombinant OGTase. ... Related to the preparation of a putative inhibitor of β-N-acetylglucosaminidases was the synthesis of a conformationally rigid carbocycle derivative of PUGNAc 4, along with two other derivatives 5 and 6. These compounds were also tested against four β-N-acetylglucosaminidases and a recombinant OGTase. ... Finally, the synthesis of a mechanism-based inhibitor of family GH3 β-Nacetylglucosaminidases, namely 2-acetamido-2-deoxy-5-fluoro-β-D-glucopyranosyl fluoride 7, is described. The incorporation of an azido moiety allows for the utilisation of 8 as an effective probe of β-N-acetylglucosaminidases. ...
| Identifer | oai:union.ndltd.org:ADTP/221389 |
| Date | January 2007 |
| Creators | Scaffidi, Adrian |
| Publisher | University of Western Australia. School of Biomedical, Biomolecular and Chemical Sciences |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Adrian Scaffidi, http://www.itpo.uwa.edu.au/UWA-Computer-And-Software-Use-Regulations.html |
Page generated in 0.0014 seconds