HaloTag‐targeted sirtuin‐rearranging ligand (SirReal) for the development of proteolysis‐targeting chimeras (PROTACs) against the lysine deacetylase sirtuin 2 (Sirt2)
Abstract: We have discovered the sirtuin‐rearranging ligands (SirReals) as a novel class of highly potent and selective inhibitors of the NAD+‐dependent lysine deacetylase sirtuin 2 (Sirt2). In previous studies, conjugation of a SirReal with a ligand for the E3 ubiquitin ligase cereblon to form a so‐called proteolysis‐targeting chimera (PROTAC) enabled small‐molecule‐induced degradation of Sirt2. Herein, we report the structure‐based development of a chloroalkylated SirReal that induces the degradation of Sirt2 mediated by Halo‐tagged E3 ubiquitin ligases. Using this orthogonal approach for Sirt2 degradation, we show that other E3 ligases than cereblon, such as the E3 ubiquitin ligase parkin, can also be harnessed for small‐molecule‐induced Sirt2 degradation, thereby emphasizing the great potential of parkin to be used as an E3 ligase for new PROTACs approaches. Thus, our study provides new insights into targeted protein degradation in general and Sirt2 degradation in particular
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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ChemBioChem. - 21, 23 (2020) , 3371-3376, ISSN: 1439-7633
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2021
- Creator
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Schiedel, Matthias
Lehotzky, Attila
Szunyogh, Sándor
Oláh, Judit
Hammelmann, Sören
Wössner, Natalie
Robaa, Dina
Einsle, Oliver
Sippl, Wolfgang
Ovádi, Judit
Jung, Manfred
- DOI
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10.1002/cbic.202000351
- URN
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urn:nbn:de:bsz:25-freidok-1939372
- Rights
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Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:22 AM CEST
Data provider
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Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Schiedel, Matthias
- Lehotzky, Attila
- Szunyogh, Sándor
- Oláh, Judit
- Hammelmann, Sören
- Wössner, Natalie
- Robaa, Dina
- Einsle, Oliver
- Sippl, Wolfgang
- Ovádi, Judit
- Jung, Manfred
- Universität
Time of origin
- 2021
Other Objects (12)
HaloTag‐Targeted Sirtuin‐Rearranging Ligand (SirReal) for the Development of Proteolysis‐Targeting Chimeras (PROTACs) against the Lysine Deacetylase Sirtuin 2 (Sirt2) **
Design, Synthese und Charakterisierung neuer Sirtuin Inhibitoren
Proteolysis targeting chimeras (PROTACs) for epigenetics research
Molecular Modelling Untersuchungen zum Bindungsverhalten von Histamin H2- und H3-Rezeptor-Liganden
Application of computer-based methods to guide the development of novel sirtuin inhibitors : [kumulative Dissertation]
Virtual screening and molecular modeling studies applied to discover novel sirtuin modulators and cholinesterase inhibitors : [kumulative Dissertation]
Epigenetic targets in drug discovery
Identification of bichalcones as sirtuin inhibitors by virtual screening and in vitro testing
Investigations of sirtuin metabolism
Sirtuin 1 inhibiting thiocyanates (S1th) - a new class of isotype selective inhibitors of NAD+ dependent lysine deacetylases
Design, synthesis and biological characterization of histone deacetylase 8 (HDAC8) proteolysis targeting chimeras (PROTACs) with anti-neuroblastoma activity
Kinetische Untersuchungen humaner Sirtuin-Isoformen
HaloTag‐Targeted Sirtuin‐Rearranging Ligand (SirReal) for the Development of Proteolysis‐Targeting Chimeras (PROTACs) against the Lysine Deacetylase Sirtuin 2 (Sirt2) **
Design, Synthese und Charakterisierung neuer Sirtuin Inhibitoren
Proteolysis targeting chimeras (PROTACs) for epigenetics research
Molecular Modelling Untersuchungen zum Bindungsverhalten von Histamin H2- und H3-Rezeptor-Liganden
Application of computer-based methods to guide the development of novel sirtuin inhibitors : [kumulative Dissertation]
Virtual screening and molecular modeling studies applied to discover novel sirtuin modulators and cholinesterase inhibitors : [kumulative Dissertation]
Epigenetic targets in drug discovery
Identification of bichalcones as sirtuin inhibitors by virtual screening and in vitro testing
Investigations of sirtuin metabolism
Sirtuin 1 inhibiting thiocyanates (S1th) - a new class of isotype selective inhibitors of NAD+ dependent lysine deacetylases
Design, synthesis and biological characterization of histone deacetylase 8 (HDAC8) proteolysis targeting chimeras (PROTACs) with anti-neuroblastoma activity
Kinetische Untersuchungen humaner Sirtuin-Isoformen
HaloTag‐Targeted Sirtuin‐Rearranging Ligand (SirReal) for the Development of Proteolysis‐Targeting Chimeras (PROTACs) against the Lysine Deacetylase Sirtuin 2 (Sirt2) **
Design, Synthese und Charakterisierung neuer Sirtuin Inhibitoren
Proteolysis targeting chimeras (PROTACs) for epigenetics research
Molecular Modelling Untersuchungen zum Bindungsverhalten von Histamin H2- und H3-Rezeptor-Liganden
Application of computer-based methods to guide the development of novel sirtuin inhibitors : [kumulative Dissertation]
Virtual screening and molecular modeling studies applied to discover novel sirtuin modulators and cholinesterase inhibitors : [kumulative Dissertation]
Epigenetic targets in drug discovery
Identification of bichalcones as sirtuin inhibitors by virtual screening and in vitro testing
Investigations of sirtuin metabolism
Sirtuin 1 inhibiting thiocyanates (S1th) - a new class of isotype selective inhibitors of NAD+ dependent lysine deacetylases
Design, synthesis and biological characterization of histone deacetylase 8 (HDAC8) proteolysis targeting chimeras (PROTACs) with anti-neuroblastoma activity