7u8z | pdb_00007u8z

Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 (CD2) complexed with fluorinated peptoid inhibitor

spinqualitylabelsall models 7u8z, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7u8z is a 4 chain structure with sequence from Danio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.85Å Ligands: ACT, EDO, GOL, K, M0I, MLI, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A7YT55_DANRE Publication Abstract from PubMed Using a microwave-assisted protocol, we synthesized 16 peptoid-capped HDAC inhibitors (HDACi) with fluorinated linkers and identified two hit compounds. In biochemical and cellular assays, 10h stood out as a potent unselective HDACi with remarkable cytotoxic potential against different therapy-resistant leukemia cell lines. 10h demonstrated prominent antileukemic activity with low cytotoxic activity toward healthy cells. Moreover, 10h exhibited synergistic interactions with the DNA methyltransferase inhibitor decitabine in AML cell lines. The comparison of crystal structures of HDAC6 complexes with 10h and its nonfluorinated counterpart revealed a similar occupation of the L1 loop pocket but slight differences in zinc coordination. The substitution pattern of the acyl residue turned out to be crucial in terms of isoform selectivity. The introduction of an isopropyl group onto the phenyl ring provided the highly HDAC6-selective inhibitor 10p, which demonstrated moderate synergy with decitabine and exceeded the HDAC6 selectivity of tubastatin A. Development of Fluorinated Peptoid-Based Histone Deacetylase (HDAC) Inhibitors for Therapy-Resistant Acute Leukemia.,Ressing N, Schliehe-Diecks J, Watson PR, Sonnichsen M, Cragin AD, Scholer A, Yang J, Schaker-Hubner L, Borkhardt A, Christianson DW, Bhatia S, Hansen FK J Med Chem. 2022 Nov 9. doi: 10.1021/acs.jmedchem.2c01418. PMID:36351184 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone deacetylase 3D structures

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