Open Collections

UBC Faculty Research and Publications

N-Alkylated Iminosugar Based Ligands: Synthesis and Inhibition of Human Lysosomal β-Glucocerebrosidase Wolfsgruber, Andreas; Thonhofer, Martin; Weber, Patrick; Nasseri, Seyed A.; Fischer, Roland; Schalli, Michael; Stütz, Arnold E.; Withers, Stephen G.; Wrodnigg, Tanja M.

Abstract

The scope of a series of N-alkylated iminosugar based inhibitors in the d-gluco as well as d-xylo configuration towards their interaction with human lysosomal β-glucocerebrosidase has been evaluated. A versatile synthetic toolbox has been developed for the synthesis of N-alkylated iminosugar scaffolds conjugated to a variety of terminal groups via a benzoic acid ester linker. The terminal groups such as nitrile, azide, alkyne, nonafluoro-tert-butyl and amino substituents enable follow-up chemistry as well as visualisation experiments. All compounds showed promising inhibitory properties as well as selectivities for β-glucosidases, some exhibiting activities in the low nanomolar range for β-glucocerebrosidase.

Item Metadata

Title
N-Alkylated Iminosugar Based Ligands: Synthesis and Inhibition of Human Lysosomal β-Glucocerebrosidase
Creator
Wolfsgruber, Andreas; Thonhofer, Martin; Weber, Patrick; Nasseri, Seyed A.; Fischer, Roland; Schalli, Michael; Stütz, Arnold E.; Withers, Stephen G.; Wrodnigg, Tanja M.
Publisher
Multidisciplinary Digital Publishing Institute
Date Issued
2020-10-11
Description
The scope of a series of N-alkylated iminosugar based inhibitors in the d-gluco as well as d-xylo configuration towards their interaction with human lysosomal β-glucocerebrosidase has been evaluated. A versatile synthetic toolbox has been developed for the synthesis of N-alkylated iminosugar scaffolds conjugated to a variety of terminal groups via a benzoic acid ester linker. The terminal groups such as nitrile, azide, alkyne, nonafluoro-tert-butyl and amino substituents enable follow-up chemistry as well as visualisation experiments. All compounds showed promising inhibitory properties as well as selectivities for β-glucosidases, some exhibiting activities in the low nanomolar range for β-glucocerebrosidase.
Subject
N-alkylated iminosugars; inhibitors for β-glucocerebrosidase; tools for glycoprocessing enzymes; β-glucosidase inhibitors; glycomimetics
Genre
Article
Type
Text
Language
eng
Date Available
2020-11-26
Provider
Vancouver : University of British Columbia Library
Rights
CC BY 4.0
DOI
10.14288/1.0395070
URI
http://hdl.handle.net/2429/76590
Affiliation
Science, Faculty of; Non UBC; Chemistry, Department of
Citation
Molecules 25 (20): 4618 (2020)
Publisher DOI
10.3390/molecules25204618
Peer Review Status
Reviewed
Scholarly Level
Faculty
Rights URI
https://creativecommons.org/licenses/by/4.0/
Aggregated Source Repository
DSpace

Item Media

Item Citations and Data

Rights

CC BY 4.0