The development of tools to study carbohydrate-processing enzymes

[Truncated] Carbohydrates perform a diverse range of functions in biological systems, including roles in metabolism, modulating structural integrity, and mediating intra-cellular and extracellular signalling. This range of roles can be performed by carbohydrates because of the overwhelming structural diversity of these molecules, and a variety of enzymes are required to process carbohydrates because of this structural diversity. The specific biological roles of carbohydrate-processing enzymes are of significant interest for a better understanding of the biological systems in which they operate, and as well, many carbohydrate-processing enzymes are of interest for the disease states that are associated with their dysfunction.

This thesis is divided into two parts, which detail various efforts to design tools to study carbohydrate-processing enzymes and demonstrate some applications of these tools. The first part of this thesis details investigations into the development of some potential inhibitors and substrates of glycoside hydrolases and is divided into three chapters.

The first chapter provides a general overview of glycoside hydrolases, and outlines previous efforts to develop inhibitors of these enzymes.

The second chapter provides an account of the design and synthesis of the L-fucoconfigured hydroximolactone and a suite of N-O-functionalised derivatives of this compound as potential inhibitors of α-L-fucosidases. The compounds were assayed against bovine kidney α-L-fucosidase for potency and the relationship between the structures of these compounds and their relative potencies was assessed.