0586126 - MBÚ 2025 RIV NL eng J - Článek v odborném periodiku
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
Grant CEP: GA ČR(CZ) GF21-01948L; GA MŠMT(CZ) EH22_008/0004597
Výzkumná infrastruktura: e-INFRA CZ - 90140; CERIT-SC - 90085; CESNET II - 90042
Institucionální podpora: RVO:61388971
Klíčová slova: Glycosidase * Inhibition * Inhibition * O-GlcNAcase * Hexosaminidase * Diaminocyclopentane * Tau protein * Alzheimer’s disease
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4.5, rok: 2023 ; AIS: 0.659, rok: 2023
Způsob publikování: Open access
Web výsledku:
https://www.sciencedirect.com/science/article/pii/S0045206824003572DOI: https://doi.org/10.1016/j.bioorg.2024.107452

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.
Trvalý link: https://hdl.handle.net/11104/0353722