Diaminocyclopentane-derived O-GlcNAcase inhibitors for combating tau hyperphosphorylation in Alzheimer's disease

Patrick Weber; Zuzana Mészáros; Denis  Jagecic; Valentina  Hribljan; Dinko  Mitrecic; Pavla Bojarova; Kristyna Slamova; Jiri Vrba; Natalia Kulik; Vladimir Kren; Arnold Stütz

doi:10.1039/D2CC02712G

Diaminocyclopentane-derived O-GlcNAcase inhibitors for combating tau hyperphosphorylation in Alzheimer's disease

Patrick Weber, Zuzana Mészáros, Denis Jagecic, Valentina Hribljan, Dinko Mitrecic, Pavla Bojarova, Kristyna Slamova, Jiri Vrba, Natalia Kulik, Vladimir Kren^*, Arnold Stütz

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

We developed potent and selective aminocyclopentane-derived inhibitors of human O-N-acetyl-β-d-glucosaminidase (OGA) implicated in Alzheimer's disease. For example compound 13 was a nanomolar OGA inhibitor with 92 000-fold selectivity over human HexB. It was non-toxic and increased protein O-GlcNAcylation in the culture of murine neural cells, showing new alternatives in the treatment of tauopathies.

Original language	English
Pages (from-to)	8838-8841
Number of pages	4
Journal	Chemical Communications
Volume	58
Issue number	63
DOIs	https://doi.org/10.1039/D2CC02712G
Publication status	Published - 12 Jul 2022

ASJC Scopus subject areas

Electronic, Optical and Magnetic Materials
Ceramics and Composites
Metals and Alloys
Materials Chemistry
Surfaces, Coatings and Films
General Chemistry
Catalysis

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10.1039/D2CC02712G

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abstract = "We developed potent and selective aminocyclopentane-derived inhibitors of human O-N-acetyl-β-d-glucosaminidase (OGA) implicated in Alzheimer's disease. For example compound 13 was a nanomolar OGA inhibitor with 92 000-fold selectivity over human HexB. It was non-toxic and increased protein O-GlcNAcylation in the culture of murine neural cells, showing new alternatives in the treatment of tauopathies.",

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T1 - Diaminocyclopentane-derived O-GlcNAcase inhibitors for combating tau hyperphosphorylation in Alzheimer's disease

AU - Weber, Patrick

AU - Mészáros, Zuzana

AU - Jagecic, Denis

AU - Hribljan, Valentina

AU - Mitrecic, Dinko

AU - Bojarova, Pavla

AU - Slamova, Kristyna

AU - Vrba, Jiri

AU - Kulik, Natalia

AU - Kren, Vladimir

AU - Stütz, Arnold

PY - 2022/7/12

Y1 - 2022/7/12

N2 - We developed potent and selective aminocyclopentane-derived inhibitors of human O-N-acetyl-β-d-glucosaminidase (OGA) implicated in Alzheimer's disease. For example compound 13 was a nanomolar OGA inhibitor with 92 000-fold selectivity over human HexB. It was non-toxic and increased protein O-GlcNAcylation in the culture of murine neural cells, showing new alternatives in the treatment of tauopathies.

AB - We developed potent and selective aminocyclopentane-derived inhibitors of human O-N-acetyl-β-d-glucosaminidase (OGA) implicated in Alzheimer's disease. For example compound 13 was a nanomolar OGA inhibitor with 92 000-fold selectivity over human HexB. It was non-toxic and increased protein O-GlcNAcylation in the culture of murine neural cells, showing new alternatives in the treatment of tauopathies.

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DO - 10.1039/D2CC02712G

M3 - Article

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SN - 1359-7345

VL - 58

SP - 8838

EP - 8841

JO - Chemical Communications

JF - Chemical Communications

IS - 63

ER -

Diaminocyclopentane-derived O-GlcNAcase inhibitors for combating tau hyperphosphorylation in Alzheimer's disease

Abstract

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