N-alkylated iminosugar based ligands: Synthesis and inhibition of human lysosomal β-glucocerebrosidase

Andreas Wolfsgruber, Martin Thonhofer, Patrick Weber, Seyed A. Nasseri, Roland Fischer, Michael Schalli, Arnold E. Stütz, Stephen G. Withers, Tanja M. Wrodnigg*

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number4618
JournalMolecules
Volume25
Issue number20
DOIs
Publication statusPublished - Oct 2020

Keywords

  • Glycomimetics
  • Inhibitors for β-glucocerebrosidase
  • N-alkylated iminosugars
  • Tools for glycoprocessing enzymes
  • β-glucosidase inhibitors

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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