The development of chemical tools to study carbohydrate-processing enzymes

Mitchell Hattie

Research output: ThesisDoctoral Thesis

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Abstract

[Truncated] Carbohydrates are involved in a variety of diverse biological functions; most interestingly is the critical role they play in an array of inter- and intra-cellular signalling, recognition, and regulation roles, which have a large impact on human health. One of the main reasons why carbohydrates are involved in such diverse functions is due to the expansive structural diversity that carbohydrate motifs display, and as such, a complementary expanse of carbohydrate-processing enzymes exist inorder to help these varied carbohydrates perform their respective functions.

This thesis focuses on a particular group of carbohydrate-processing enzymes, namely the N-acetylhexosaminidases, which are a type of glycosidase that cleave N-acetylhexosamine residues in a range of prokaryotic and eukaryotic systems. Understanding the roles that N-acetylhexosaminidases play in these systems is of great importance, and as such, this thesis details the efforts to design, prepare, and demonstrate the application of varied chemical tools to better understand such roles.

The first chapter provides a general overview of N-acetylhexosaminidases, and outlines previous efforts to develop small molecule inhibitors of these enzymes.

The second chapter details an investigation into the inhibitory properties of PUGNAc (15), a well-known potent inhibitor of a variety of N-acetylhexosaminidases.A suite of PUGNAc analogues (62) were synthesised and evaluated as potential inhibitors of OGA, HexB, and NAGLU, with certain analogues that showed goodselectivity for HexB over OGA and NAGLU further derivatised and evaluated.

Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - Sep 2015

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