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Studies towards finding selective substrates for human β-glucosidases

Resource type
Thesis type
(Thesis) M.Sc.
Date created
2021-12-23
Authors/Contributors
Abstract
Humans have three types of β-glucosidases (GBA) enzymes named GBA1, GBA2, and GBA3 that break down glucosylceramide (GlcCer). Studies have suggested that GBA2 is involved in Gaucher disease via feedback mechanism with GBA1, and lack of GBA2 activity leads to other neurodegenerative diseases. However, currently with no selective substrate probe developed for GBA2, making it difficult to study the enzyme activity, the role of GBA2 in pathogenesis of the diseases remains unclear. To find GBA2 selective substrates, the substrate specificity of GBA enzymes was investigated by preparing a series of mono-substituted deoxyfluoro and deoxy analogs of the substrate and testing the compounds with GBA enzymes to obtain Michaelis-Menten parameters, which allowed the evaluation of the affinity of each compound against each enzyme. This approach led to a compound that shows selectivity towards GBA2, which can be further developed into a cell lysate probe for brain cells.
Document
Extent
104 pages.
Identifier
etd21751
Copyright statement
Copyright is held by the author(s).
Permissions
This thesis may be printed or downloaded for non-commercial research and scholarly purposes.
Supervisor or Senior Supervisor
Thesis advisor: Vocadlo, David
Thesis advisor: Bennet, Andrew
Language
English
Member of collection
Download file Size
etd21751.pdf 2.56 MB

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