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@ARTICLE{Darwish:182156,
author = {S. Darwish and T. Heimburg and J. Ridinger$^*$ and D. Herp
and M. Schmidt and C. Romier and M. Jung and I. Oehme$^*$
and W. Sippl},
title = {{S}ynthesis, {B}iochemical, and {C}ellular {E}valuation of
{HDAC}6 {T}argeting {P}roteolysis {T}argeting {C}himeras.},
journal = {Methods in molecular biology},
volume = {2589},
issn = {1064-3745},
address = {[Heidelberg]},
publisher = {[Springer]},
reportid = {DKFZ-2022-02467},
isbn = {978-1-0716-2787-7 (print)},
pages = {179-193},
year = {2023},
abstract = {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.},
keywords = {Epigenetic proteins (Other) / Histone deacetylase 6 (Other)
/ Proteolysis-targeting chimeras (Other)},
cin = {B310 / HD01},
ddc = {570},
cid = {I:(DE-He78)B310-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)3 / PUB:(DE-HGF)16},
pubmed = {pmid:36255625},
doi = {10.1007/978-1-0716-2788-4_12},
url = {https://inrepo02.dkfz.de/record/182156},
}