Unknown

Dataset Information

0

N-Alkylated Iminosugar Based Ligands: Synthesis and Inhibition of Human Lysosomal ?-Glucocerebrosidase.

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 ?-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 ?-glucosidases, some exhibiting activities in the low nanomolar range for ?-glucocerebrosidase.

SUBMITTER: Wolfsgruber A 

PROVIDER: S-EPMC7594070 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

<i>N</i>-Alkylated Iminosugar Based Ligands: Synthesis and Inhibition of Human Lysosomal β-Glucocerebrosidase.

Wolfsgruber Andreas A   Thonhofer Martin M   Weber Patrick P   Nasseri Seyed A SA   Fischer Roland R   Schalli Michael M   Stütz Arnold E AE   Withers Stephen G SG   Wrodnigg Tanja M TM  

Molecules (Basel, Switzerland) 20201011 20

The scope of a series of <i>N</i>-alkylated iminosugar based inhibitors in the d-<i>gluco</i> as well as d-<i>xylo</i> configuration towards their interaction with human lysosomal β-glucocerebrosidase has been evaluated. A versatile synthetic toolbox has been developed for the synthesis of <i>N</i>-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-<i>tert</i>-butyl and amino su  ...[more]

Similar Datasets

Unknown Synthesis of modified 1,5-imino-d-xylitols as ligands for lysosomal <i>β</i>-glucocerebrosidase.
| S-EPMC6534063 | biostudies-literature
Unknown Non-iminosugar glucocerebrosidase small molecule chaperones.
| S-EPMC3351140 | biostudies-literature
Unknown Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters.
| S-EPMC7694328 | biostudies-literature
Unknown Iminosugar C-glycoside analogues of ?-D-GlcNAc-1-phosphate: synthesis and bacterial transglycosylase inhibition.
| S-EPMC4168788 | biostudies-literature
Unknown Effects of pH and iminosugar pharmacological chaperones on lysosomal glycosidase structure and stability.
| S-EPMC2699628 | biostudies-literature
Unknown Assessment of Target Engagement in a First-in-Human Trial with Sinbaglustat, an Iminosugar to Treat Lysosomal Storage Disorders.
| S-EPMC7993281 | biostudies-literature
Unknown Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores.
| S-EPMC4077385 | biostudies-other
Unknown The association between mutations in the lysosomal protein glucocerebrosidase and parkinsonism.
| S-EPMC2736332 | biostudies-literature
Unknown Lysosomal Enzyme Glucocerebrosidase Protects against A?1-42 Oligomer-Induced Neurotoxicity.
| S-EPMC4668030 | biostudies-literature
Unknown Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells.
| S-EPMC3999713 | biostudies-literature