141023-00-9Relevant articles and documents
A Fluorescence-Lifetime-Based Binding Assay for Class IIa Histone Deacetylases
Meyners, Christian,Mertens, Monique,Wessig, Pablo,Meyer-Almes, Franz-Josef
, p. 3107 - 3116 (2017/03/13)
Class IIa histone deacetylases (HDACs) show extremely low enzymatic activity and no commonly accepted endogenous substrate is known today. Increasing evidence suggests that these enzymes exert their effect rather through molecular recognition of acetylated proteins and recruiting other proteins like HDAC3 to the desired target location. Accordingly, class IIa HDACs like bromodomains have been suggested to act as “Readers” of acetyl marks, whereas enzymatically active HDACs of class I or IIb are called “Erasers” to highlight their capability to remove acetyl groups from acetylated histones or other proteins. Small-molecule ligands of class IIa histone deacetylases (HDACs) have gained tremendous attention during the last decade and have been suggested as pharmaceutical targets in several indication areas such as cancer, Huntington's disease and muscular atrophy. Up to now, only enzyme activity assays with artificial chemically activated trifluoroacetylated substrates are in use for the identification and characterization of new active compounds against class IIa HDACs. Here, we describe the first binding assay for this class of HDAC enzymes that involves a simple mix-and-measure procedure and an extraordinarily robust fluorescence lifetime readout based on [1,3]dioxolo[4,5-f]benzodioxole-based ligand probes. The principle of the assay is generic and can also be transferred to class I HDAC8.
Highly selective trifluoroacetic ester/ketone metathesis: An efficient approach to trifluoromethyl ketones and esters
Zhou, Yuhan,Yang, Dongmei,Luo, Gen,Zhao, Yilong,Luo, Yi,Xue, Na,Qu, Jingping
, p. 4668 - 4674 (2014/06/23)
A highly selective and atom efficient 'trifluoroacetic ester/ketone metathesis' has been sincerely witnessed. Enolizable alkyl (at least two non-hydrogen atoms) aryl ketones were found to react readily with ethyl trifluoroacetate under the promotion of NaH to afford trifluoroacetic ester/ketone exchange products, trifluoromethyl ketones (TFMKs), and aromatic acid esters, which were quite different from the general Claisen condensation products, 1,3-diketones. The outcome of the reaction between ketone and ethyl trifluoroacetate is strongly related to the structures of substrates, the steric congestion caused by alkyl group is in favor of the C-C bond cleavage. DFT investigation further disclosed that the metathesis reaction was a kinetically favored pathway. Using only a slight excess of cheap trifluoromethylation reagent, simple operation and mild conditions make it a practical method for preparation of TFMKs on large scale, as well as a new choice of converting aryl alkyl ketones to aromatic acid esters.
A New and Efficient Synthesis of Trifluoromethyl Ketones from Carboxylic Acids. Part I.
Boivin, Jean,El Kaim, Laurent,Zard, Samir Z.
, p. 2573 - 2584 (2007/10/02)
Trifluoromethyl ketones can be prepared in good yield from primary carboxylic acid chlorides by reaction with pyridine and trifluoroacetic anhydride followed by aqueous work up.
