Highly functionalized diaminocyclopentanes: A new route to potent and selective inhibitors of human O-GlcNAcase.

Alzheimer’s disease Diaminocyclopentane Glycosidase inhibition O-GlcNAcase

Journal

Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703

Informations de publication

Date de publication:
11 2023
Historique:
received: 15 05 2023
revised: 11 08 2023
accepted: 27 08 2023
medline: 18 9 2023
pubmed: 5 9 2023
entrez: 4 9 2023
Statut: ppublish

Résumé

A new class of compounds inhibiting de-O-glycosylation of proteins has been identified. Highly substituted diaminocyclopentanes are impressively selective reversible non-transition state O-β-N-acetyl-d-glucosaminidase (O-GlcNAcase) inhibitors. The ease of preparative access and remarkable biological activities provide highly viable leads for the development of anti-tau-phosphorylation agents with a view to eventually ameliorating Alzheimer's disease.

Identifiants

pubmed: 37666109
pii: S0045-2068(23)00480-7
doi: 10.1016/j.bioorg.2023.106819
pii:
doi:

Substances chimiques

hexosaminidase C EC 3.2.1.50
beta-N-Acetylhexosaminidases EC 3.2.1.52
Hexosaminidases EC 3.2.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

106819

Subventions

Organisme : Austrian Science Fund FWF
ID : I 5236
Pays : Austria

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Patrick Weber (P)

Glycogroup, Institute of Chemistry and Technology of Biobased Systems, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria. Electronic address: patrick.weber@tugraz.at.

Zuzana Mészáros (Z)

Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ 14200, Prague 4, Czech Republic.

Pavla Bojarová (P)

Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ 14200, Prague 4, Czech Republic.

Manuel Ebner (M)

Glycogroup, Institute of Chemistry and Technology of Biobased Systems, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

Roland Fischer (R)

Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

Vladimír Křen (V)

Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ 14200, Prague 4, Czech Republic.

Natalia Kulik (N)

Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ 14200, Prague 4, Czech Republic.

Philipp Müller (P)

Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

Miluše Vlachová (M)

Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ 14200, Prague 4, Czech Republic.

Kristýna Slámová (K)

Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ 14200, Prague 4, Czech Republic.

Arnold E Stütz (AE)

Glycogroup, Institute of Chemistry and Technology of Biobased Systems, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

Martin Thonhofer (M)

Glycogroup, Institute of Chemistry and Technology of Biobased Systems, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

Ana Torvisco (A)

Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

Tanja M Wrodnigg (TM)

Glycogroup, Institute of Chemistry and Technology of Biobased Systems, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

Andreas Wolfsgruber (A)

Glycogroup, Institute of Chemistry and Technology of Biobased Systems, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

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Classifications MeSH