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 language | English |
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Article number | 4618 |
Journal | Molecules |
Volume | 25 |
Issue number | 20 |
DOIs | |
Publication status | Published - 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