TY  - JOUR
AU  - Darwish, Salma
AU  - Heimburg, Tino
AU  - Ridinger, Johannes
AU  - Herp, Daniel
AU  - Schmidt, Matthias
AU  - Romier, Christophe
AU  - Jung, Manfred
AU  - Oehme, Ina
AU  - Sippl, Wolfgang
TI  - Synthesis, Biochemical, and Cellular Evaluation of HDAC6 Targeting Proteolysis Targeting Chimeras.
JO  - Methods in molecular biology
VL  - 2589
SN  - 1064-3745
CY  - [Heidelberg]
PB  - [Springer]
M1  - DKFZ-2022-02467
SN  - 978-1-0716-2787-7 (print)
SP  - 179-193
PY  - 2023
AB  - Histone deacetylases are considered promising epigenetic targets for chemical protein degradation due to their diverse roles in physiological cellular functions and in the diseased state. Proteolysis-targeting chimeras (PROTACs) are bifunctional molecules that hijack the cell's ubiquitin-proteasome system (UPS). One of the promising targets for this approach is histone deacetylase 6 (HDAC6), which is highly expressed in several types of cancers and is linked to the aggressiveness of tumors. In the present work, we describe the synthesis of HDAC6 targeting PROTACs based on previously synthesized benzohydroxamates selectively inhibiting HDAC6 and how to assess their activities in different biochemical in vitro assays and in cellular assays. HDAC inhibition was determined using fluorometric assays, while the degradation ability of the PROTACs was assessed using western blot analysis.
KW  - Epigenetic proteins (Other)
KW  - Histone deacetylase 6 (Other)
KW  - Proteolysis-targeting chimeras (Other)
LB  - PUB:(DE-HGF)3 ; PUB:(DE-HGF)16
C6  - pmid:36255625
DO  - DOI:10.1007/978-1-0716-2788-4_12
UR  - https://inrepo02.dkfz.de/record/182156
ER  -