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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

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N-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 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 su ...[more]

PMID: 33050585

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