719270-08-3Relevant academic research and scientific papers
Design, synthesis, docking, and biological evaluation of novel diazide-containing isoxazole- and pyrazole-based histone deacetylase probes
Neelarapu, Raghupathi,Holzle, Denise L.,Velaparthi, Subash,Bai, He,Brunsteiner, Michael,Blond, Sylvie Y.,Petukhov, Pavel A.
experimental part, p. 4350 - 4364 (2011/09/16)
The design, synthesis, docking, and biological evaluation of novel potent HDAC3 and HDAC8 isoxazole- and pyrazole-based diazide probes suitable for binding ensemble profiling with photoaffinity labeling (BEProFL) experiments in cells is described. Both the isoxazole- and pyrazole-based probes exhibit low nanomolar inhibitory activity against HDAC3 and HDAC8, respectively. The pyrazole-based probe 3f appears to be one of the most active HDAC8 inhibitors reported in the literature with an IC50 of 17 nM. Our docking studies suggest that unlike the isoxazole-based ligands the pyrazole-based ligands are flexible enough to occupy the second binding site of HDAC8. Probes/inhibitors 2b, 3a, 3c, and 3f exerted the antiproliferative and neuroprotective activities at micromolar concentrations through inhibition of nuclear HDACs, indicating that they are cell permeable and the presence of an azide or a diazide group does not interfere with the neuroprotection properties, or enhance cellular cytotoxicity, or affect cell permeability.
Novel bifunctional probe for radioisotope-free photoaffinity labeling: Compact structure comprised of photospecific ligand ligation and detectable tag anchoring units
Hosoya, Takamitsu,Hiramatsu, Toshiyuki,Ikemoto, Takaaki,Nakanishi, Masayuki,Aoyama, Hiroshi,Hosoya, Ayako,Iwata, Tomoya,Maruyama, Kei,Endo, Makoto,Suzuki, Masaaki
, p. 637 - 641 (2007/10/03)
A novel method for radioisotope-free photoaffinity labeling was developed, in which a bifunctional ligand is connected to a target protein by activation of a photoreactive group, such as an aromatic azido or 3-trifluoromethyl-3H-diazirin-3-yl group, and identification of the ligated product is achieved by anchoring of a detectable tag through the Staudinger-Bertozzi reaction with an alkyl azido moiety that survives photolysis. The chemical ground of this method was confirmed using model compounds with the bifunctional group under photoirradiation in the presence of trapping agents for reactive intermediates. The utility of the method has been demonstrated by specific labeling of the catalytic portion of human HMG-CoA reductase.
