Promotores: H.S. Overkleeft, G.A. van der Marel, Co-promotor: B.I. Florea
|Links||Thesis in Leiden Repository|
Glycoside hydrolases (GHs), enzymes that catalyze the hydrolytic cleavage of glycosidic bonds, receive continuing interest both in fundamental and applied biology and biomedicine. Lysosomal storage disorders (LSDs) are caused by inborn metabolic errors due to deficiency in specific lysosomal enzymes, most commonly GHs. Diagnosis and treatment of LSDs require regular quantification of the active lysosomal enzymes in patient tissues. Activity-based protein profiling (ABPP) has emerged in the past decades as a powerful technique to study enzyme families in cell extracts and living tissues. Originally developed for serine hydrolases and cysteine proteases, various enzyme classes can be studied by means of ABPP today, including retaining GHs. The research described in this thesis focused on expanding the field of activity-based glycosidase profiling through the development of functional and configurationa l analog ues of cyclophellitol aziridine as activity-based probes (ABPs) for various retaining glycoside hydrolases (GHs), namely α-L-fucosidases, β-glucosidases, α-glucosidases and β-glucuronidases (Figure 1). Attention is focused on the design and synthesis of the cyclophellitol aziridine derivatives and their application in chemical biology studies of various retaining GHs.