Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.786517
Title: LALDI tags : ionization enhancers for mass spectrometry-based glycomics
Author: Hauser, Jacob Richard
ISNI:       0000 0004 7971 964X
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2019
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Abstract:
Carbohydrates play an important role in almost every structural and functional aspect of biology. One of the most important analytical tools for studying the structural and functional profile of native carbohydrates is mass spectrometry. However, the isolation and analysis of native glycans from their biological source is not trivial. Recently, label-assisted laser desorption/ionization mass spectrometry (LALDI-MS) has emerged as a powerful analytical tool that facilitates the selective detection of labelled substrates against a complex background of other reagents. This thesis explores the capabilities of LALDI-MS as a novel analytical tool for MS-based glycomics. Chapter 1 provides an overview of the different approaches to laser desorption/ionization mass spectrometry, the field of glycomics, and the challenges associated with analyzing glycans by mass spectrometry. Current applications of LALDI-MS are discussed in Section 1.2.2. Chapter 2 describes the development of a series of pyrene-based water-soluble ionization enhancers and investigations into their LALDI-MS sensitivity and stability. The results of these investigations highlight two novel ionization enhancing labels, which exhibit high LDI sensitivity and good MS stability, respectively. Chapter 3 describes the incorporation of the two chosen ionization enhancers from Chapter 2 into the design of novel chemical reagents for analyzing native glycans by LALDI-MS. Using these reagents, selective labelling and analysis of simple glycans was achieved using LALDI-MS, including the in situ labelling and direct analysis of lactose from cow's milk. Chapter 4 describes the development of a straightforward and readily scalable synthesis of 6-amino-2-cyanobenzothiazole via a 1,4-diazabicyclo[2.2.2]octane-catalyzed cyanation. This procedure allows the synthesis of the final product to be achieved in high purity at a multigram scale, requiring only filtrations and recrystallization for purification of each intermediate. Overall, this thesis demonstrates the application of LALDI-MS as a tool for studying native carbohydrates.
Supervisor: Bon, Robin ; Warriner, Stuart Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.786517  DOI: Not available
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