Synthesis, Biochemical, and Cellular Evaluation of HDAC6 Targeting Proteolysis Targeting Chimeras.
Fiche publication
Date publication
janvier 2023
Journal
Methods in molecular biology (Clifton, N.J.)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROMIER Christophe
Tous les auteurs :
Darwish S, Heimburg T, Ridinger J, Herp D, Schmidt M, Romier C, Jung M, Oehme I, Sippl W
Lien Pubmed
Résumé
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.
Mots clés
Epigenetic proteins, Histone deacetylase 6, Proteolysis-targeting chimeras
Référence
Methods Mol Biol. 2023 ;2589:179-193