Iminosugars as glucosylceramide processing enzymes inhibitors: design, synthesis and evaluation

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Iminosugars as glucosylceramide processing enzymes inhibitors: design, synthesis and evaluation

Type: Doctoral Thesis
Title: Iminosugars as glucosylceramide processing enzymes inhibitors: design, synthesis and evaluation
Author: Liu, B.
Issue Date: 2017-12-13
Keywords: Iminosugars
Deoxynojirimycin
Glucosylceramide
Glucosylceramide synthase
Lysosomal glucosylceramidase
Neutral glucosylceramidase
Abstract: This Thesis describes the design, synthesis and evaluation as glycoprocessing enzyme inhibitors of focused libraries of iminosugars. In the studies described, 1-deoxynojirimycin (DNJ), and its known N-alkylated derivatives, served as starting points. DNJ modifications presented here include alteration of the substitution pattern of the piperidine core structure; variation in the N substituent, or a combination of the two. Biological evaluation of the synthesized compounds focused on the glycoprocessing enzymes involved in glucosylceramide metabolism: glucosylceramide synthase (GCS), lysosomal glucosylceramidase (GBA1) and neutral glucosylceramidase (GBA2), and in all examples presented the inhibitory potency of newly synthesized compounds are compared with that of literature compounds.
Promotor: Supervisor: Overkleeft H.S. Co-Supervisor: Berg R.J.B.H.N. van den
Faculty: Science
University: Leiden
Handle: http://hdl.handle.net/1887/57984
 

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