Diaminocyclopentane – l-Lysine Adducts: Potent and selective inhibitors of human O-GlcNAcase

0586126 - MBÚ 2025 RIV NL eng J - Journal Article
Weber, P. - Bojarová, Pavla - Brouzdová, Jitka - Křen, Vladimír - Kulik, Natalia - Stütz, A.E. - Thonhofer, M. - Wrodnigg, T.M.
Diaminocyclopentane – l-Lysine Adducts: Potent and selective inhibitors of human O-GlcNAcase.
Bioorganic Chemistry. Roč. 148, July 2024 (2024), č. článku 107452. ISSN 0045-2068. E-ISSN 1090-2120
R&D Projects: GA ČR(CZ) GF21-01948L; GA MŠMT(CZ) EH22_008/0004597
Research Infrastructure: e-INFRA CZ - 90140; CERIT-SC - 90085; CESNET II - 90042
Institutional support: RVO:61388971
Keywords : Glycosidase * Inhibition * Inhibition * O-GlcNAcase * Hexosaminidase * Diaminocyclopentane * Tau protein * Alzheimer’s disease
OECD category: Biochemistry and molecular biology
Impact factor: 5.1, year: 2022
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S0045206824003572

A new class of compounds, namely highly substituted diaminocyclopentane-l-lysine adducts, have been discovered as potent inhibitors of O-GlcNAcase, an enzyme crucial for protein de-O-glycosylation. These inhibitors exhibit exceptional selectivity and reversibility and are the first example of human O-GlcNAcase inhibitors that are structurally related to the transition state of the rate-limiting step with the “aglycon” still in bond-length proximity. The ease of their preparation, remarkable biological activities, stability, and non-toxicity make them promising candidates for the development of anti-tau-phosphorylation agents holding significant potential for the treatment of Alzheimer's disease.
Permanent Link: https://hdl.handle.net/11104/0353722