Abstract:
:Histone deacetylases (HDACs) contribute to regulation of gene expression by mediating higher-order chromatin structures. They assemble into large multiprotein complexes that regulate activity and specificity. We report the development of small molecule probes with class IIa and pan-HDAC activity that contain photoreactive crosslinking groups and either a biotin reporter, or a terminal alkyne handle for subsequent bioorthogonal ligation. The probes retained inhibitory activity against recombinant HDAC proteins and caused an accumulation of acetylated histone and tubulin following cell treatment. The versatility of the probes has been demonstrated by their ability to photoaffinity modify HDAC targets in vitro. An affinity enrichment probe was used in conjunction with mass spectrometry proteomics to isolate HDACs and their interacting proteins in a native proteome. The performance of the probes in recombinant versus cell-based systems highlights issues for the development of chemoproteomic technologies targeting class IIa HDACs in particular.
journal_name
Mol Biosystjournal_title
Molecular bioSystemsauthors
Albrow VE,Grimley RL,Clulow J,Rose CR,Sun J,Warmus JS,Tate EW,Jones LH,Storer RIdoi
10.1039/c6mb00109bsubject
Has Abstractpub_date
2016-05-24 00:00:00pages
1781-9issue
6eissn
1742-206Xissn
1742-2051journal_volume
12pub_type
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