Neuraminidases are enzymes that cleave glycosidic linkages of sialic acid. These enzymes are involved in influenza infections as well as in many cellular processes in mammals and micro-organisms.... Show moreNeuraminidases are enzymes that cleave glycosidic linkages of sialic acid. These enzymes are involved in influenza infections as well as in many cellular processes in mammals and micro-organisms. Development of molecules that irreversibly inhibit these enzymes, as well as molecules that can covalently bind and also label these enzymes, is described in this thesis. These newly developed molecular tools can be used to study neuraminidsases. Better understanding of these enzymes could for example contribute to the timely invervention if new influenza strains emerge. Show less
Glycosidases are important enzymes in the turnover of polysaccharides and glycoconjugates, and are involved in a range of human pathologies including genetic disorders such as Gaucher and Pompe... Show moreGlycosidases are important enzymes in the turnover of polysaccharides and glycoconjugates, and are involved in a range of human pathologies including genetic disorders such as Gaucher and Pompe disease, but also in various cancers. The discovery of potent and selective glycosidase inhibitors for fundamental glycobiology studies and as leads for drug discovery requires access to suitable (glycomimetic) compound libraries, as well as easily applicable assays and screening formats. The research described in this Thesis was aimed to explore how covalent and irreversible glycosidase inhibitors can be applied in the screening of focused compound libraries on various glycosidases using fluorescence polarization activity-based protein profiling (FluoPol-ABPP). Show less
