196810-09-0Relevant articles and documents
Cyclization Reaction-Based Turn-on Probe for Covalent Labeling of Target Proteins
Fujita, Yuki,Ikebe, Yuka,Itoh, Toshimasa,Kojima, Hiroyuki,Ohashi, Nami,Takeuchi, Ryosuke,Yamamoto, Keiko
, p. 334 - 349 (2020/03/17)
Fluorescent molecules have contributed to basic biological research but there are currently only a limited number of probes available for the detection of non-enzymatic proteins. Here, we report turn-on fluorescent probes mediated by conjugate addition and cyclization (TCC probes). These probes react with multiple amino acids and exhibit a 36-fold greater emission intensity after reaction. We analyzed the reactions between TCC probes and nuclear receptors by electrospray ionization mass spectrometry, X-ray crystallography, spectrofluorometry, and fluorescence microscopy. In vitro analysis showed that probes consisting of a protein ligand and TCC could label vitamin D receptor and peroxisome proliferator-activated receptor γ. Moreover, we demonstrated that not only a ligand unit but also a peptide unit can label the target protein in a complex mixture. Non-enzymatic proteins are challenging targets for turn-on probes. Here, Kojima et al. report turn-on fluorescent probes mediated by conjugate addition and cyclization (TCC probes). These probes react with nuclear receptors and emit bright fluorescence after the reaction. TCC probes are potent tools for molecular imaging and chemical proteomics.
Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
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Page 3; sheet 30, (2010/02/03)
The subject invention provides pharmaceutical compounds useful in the treatment of Type II diabetes. These compounds are advantageous because they are readily metabolized by the metabolic drug detoxification systems. Particularly, thiazolidinedione analogs that have been designed to include esters within the structure of the compounds are provided. This invention is also drawn to methods of treating disorders, such as diabetes, comprising the administration of therapeutically effective compositions comprising compounds that have been designed to be metabolized by serum or intracellular hydrolases and esterases. Pharmaceutical compositions of the ester-containing thiazolidinedione analogs are also taught.
