This Thesis focuses on the design and synthesis of ADP-ribosylated compounds that can be applied in biological studies.The limitations of the contemporary methods of chemical ADP-ribosylation and a... Show moreThis Thesis focuses on the design and synthesis of ADP-ribosylated compounds that can be applied in biological studies.The limitations of the contemporary methods of chemical ADP-ribosylation and a relative scarcity of the well-defined synthetic ADP-ribosylated derivative was an incentive to undertake synthetic studies to further advance the methodologies in the bioorganic chemistry of ADP-ribosylated molecules. This Thesis aims specifically at the developing of new and improved synthetic methodologies and to synthesize advanced mono- or oligo-ADP-ribosylated biomolecules. The target compounds that are described in this Thesis are not only represent a synthetic challenge but also have great value in biology for a better understanding of ADP-ribosylation. Show less
The aim of this thesis is to explore the glycosylation of PSA as well as to study if alterations can be observed between patients with indolent and malignant PCa. For this purpose the powerful... Show moreThe aim of this thesis is to explore the glycosylation of PSA as well as to study if alterations can be observed between patients with indolent and malignant PCa. For this purpose the powerful analytical platform CE-ESI-MS(/MS) was explored with a special focus on the analysis of glycans and glycopeptides (Chapter 1). The first section of the thesis describes the different method developments implemented for the analysis of PSA with CE-ESI-MS. Namely, Chapter 2 describes that CE-ESI-MS enables to separate glycopeptides with differently linked sialic acids without any additional sample treatment, Chapter 3 shows that an introduction of a dopant enriched nitrogen gas improves the limit of detection (sensitivity) of glycopeptides and Chapter 4 introduces a novel labeling procedure of total plasma N-glycome with the hydrazide Girard’s reagent P. Chapter 5 describes the development of a PSA Glycomics Assay which allows the capture of intact PSA from patients’ urine followed by analysis with the optimized CE-ESI-MS platform (Chapters 2 and 3). Finally, Chapter 6 offers a general discussion about future developments, the potential of PSA glycosylation in the clinical setting, showing the relevance of our results and how these may contribute to further clinical applications towards personalized medicine. Show less
