Abbey, Lorna (2013) The Synthesis of Amphiphilic Glycolipids as Potential Inhibitors of Bacterial Adhesion. PhD thesis, National University of Ireland Maynooth.

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Abstract

The synthesis of glycolipids as potential anti-bacterial agents and glycolipid mimetics is the main focus of the research presented in this thesis. A variety of glycolipids based around an aspartic acid, aliphatic or aromatic scaffold were investigated. Chapter 1 describes the biological importance of glycolipids and how they can be utilised as anti-adhesion agents and immunomodulators. The concept of multivalency is also discussed, with specific examples relating to the anti-adhesion approach. A variety of O-glycolipids based around an aspartic acid scaffold were constructed in chapter 2. Based on a modular approach, a diverse range of glycolipids were synthesised. They exhibited variations in hydrocarbon chain length, number of hydrocarbon chains, connectivity of carbohydrate moiety and the carbohydrate moiety used. Although originally designed to act as immunomodulators their ability to inhibit bacterial adhesion in immunocompromised individuals was also investigated. Furthermore the glycolipids were tested as low molecular weight organogelators (LWOG), and promising results were obtained. Chapter 3 deals with the synthesis of O- and N-glycolipids built around an aliphatic core. Initially the synthesis proved problematic but success was achieved utilising DMTMM as the coupling reagent. Similarly to the aspartic acid analogues, the glycolipids exhibited variation in the chemical nature of the spacer groups used to link the carbohydrate to the aliphatic core. The O- and N-glycolipids were synthesised with a view to examine their ability to inhibit bacterial adhesion in Cystic Fibrosis (CF) patients. The synthesis of a range of glycolipids based around an aromatic core is discussed in chapter 4. Again variation in the linker utilised to connect the carbohydrate moiety and the aromatic core is explored. This time the importance of the presence of the hydrocarbon chain was also investigated. Therefore variation in the connectivity of the lipidic chain is explored, and analogues of varying hydrocarbon chain length were synthesised. The O- and N-glycolipids were synthesised as potential anti-adhesion agents in order to determine a structural activity relationship. The biological evaluation of selected glycolipids is discussed in chapter 5. Selected aspartic acid, aliphatic and aromatic glycolipids are investigated as potential inhibitors of Burkholderia multivorans adhesion to a model of lung epithelial cells of CF patients. Promising preliminary results were obtained for both a mono- and di-valent aromatic-based glycolipid.

Item Type:	Thesis (PhD)
Keywords:	Synthesis; Amphiphilic Glycolipids; Potential Inhibitors; Bacterial Adhesion;
Academic Unit:	Faculty of Science and Engineering > Chemistry
Item ID:	7685
Depositing User:	IR eTheses
Date Deposited:	06 Jan 2017 12:12
URI:
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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