Universiteit Leiden

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Proefschrift

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

This Thesis describes the design, synthesis and evaluation as glycoprocessing enzyme inhibitors of focused libraries of iminosugars.

Auteur
Liu, B.
Datum
13 december 2017
Links
Thesis in Leiden Repository

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.

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