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991.
In Situ Proteome Profiling and Bioimaging Applications of Small‐Molecule Affinity‐Based Probes Derived From DOT1L Inhibitors 下载免费PDF全文
Biwei Zhu Dr. Hailong Zhang Sijun Pan Chenyu Wang Dr. Jingyan Ge Prof. Dr. Jun‐Seok Lee Prof. Dr. Shao Q. Yao 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(23):7824-7836
DOT1L is the sole protein methyltransferase that methylates histone H3 on lysine 79 (H3K79), and is a promising drug target against cancers. Small‐molecule inhibitors of DOT1L such as FED1 are potential anti‐cancer agents and useful tools to investigate the biological roles of DOT1L in human diseases. FED1 showed excellent in vitro inhibitory activity against DOT1L, but its cellular effect was relatively poor. In this study, we designed and synthesized photo‐reactive and “clickable” affinity‐based probes (AfBPs), P1 and P2 , which were cell‐permeable and structural mimics of FED1 . The binding and inhibitory effects of these two probes against DOT1L protein were extensively investigated in vitro and in live mammalian cells (in situ). The cellular uptake and sub‐cellular localization properties of the probes were subsequently studied in live‐cell imaging experiments, and our results revealed that, whereas both P1 and P2 readily entered mammalian cells, most of them were not able to reach the cell nucleus where functional DOT1L resides. This offers a plausible explanation for the poor cellular activity of FED1 . Finally with P1 / P2 , large‐scale cell‐based proteome profiling, followed by quantitative LC‐MS/MS, was carried out to identify potential cellular off‐targets of FED1 . Amongst the more than 100 candidate off‐targets identified, NOP2 (a putative ribosomal RNA methyltransferase) was further confirmed to be likely a genuine off‐target of FED1 by preliminary validation experiments including pull‐down/Western blotting (PD/WB) and cellular thermal shift assay (CETSA). 相似文献
992.
A Pronounced Halogen Effect on the Organogelation Properties of Peripherally Halogen Functionalized Poly(benzyl ether) Dendrons 下载免费PDF全文
Prof. Dr. Yu Feng Hui Chen Zhi‐Xiong Liu Yan‐Mei He Prof. Dr. Qing‐Hua Fan 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(14):4980-4990
An interesting halogen‐substituent effect on the organogelation properties of poly(benzyl ether) dendrons is reported. A new class of poly(benzyl ether) dendrons with halo substituents decorating their periphery was synthesized and fully characterized. A systematic study on the gelation abilities, thermotropic behaviors, aggregated microstructures, and mechanical properties of self‐assembled organogels was performed to elucidate the halogen‐substituent effects on their organogelation propensity. It was found that the exact halogen substitutions on the periphery of dendrons exert a profound effect on the organogelation propensity, and dendrons G n ‐Cl (n=2, 3) and G2‐I proved to be highly efficient organogelators. The cooperation of multiple π–π, dispersive halogen, CH–π, and weak C?H ??? X hydrogen‐bonding interactions were found to be the key contributor to forming the self‐assembled gels. Dendritic organogels formed from G n ‐Cl (n=2, 3) in 1,2‐dichloroethane exhibited thixotropic‐responsive properties, and such thixotropic organogels are promising materials for future research and applications. 相似文献
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995.
Palladium‐Catalyzed Regioselective C‐Benzylation via a Rearrangement Reaction: Access to Benzyl‐Substituted Anilines 下载免费PDF全文
Dr. Manuel Amézquita‐Valencia Prof. Howard Alper 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(47):16774-16778
An unprecedented C‐benzylation rearrangement reaction, catalyzed by palladium, is reported. The reaction proceeds by rearrangement leading to the direct synthesis of para or ortho benzyl‐substituted N‐methylanilines. The product is obtained in high regioselectivity, without the need to use a ligand for the catalytic process. 相似文献
996.
Mesoporous chitosan‐immobilized iron tetrakis(4‐carboxyphenyl)porphyrin as a model of cytochrome P‐450 enzyme for oxidation of ethylbenzene 下载免费PDF全文
Mesoporous chitosan‐grafted iron tetra (4‐carboxyphenyl) porphyrin catalyst (Fe TCPP/mesp‐CTS) was prepared and investigated as a practical model for the nano‐cavity and coordinate regulation‐catalysis(CRC) function in cytochrome P‐450 enzyme. Fe TCPP/mesp‐CTS was characterized by X‐ray Diffraction (XRD), Thermogravimetry (TG), Ultraviolet–visible spectroscopy(UV‐Vis), Ultraviolet–visible– Diffuse reflectance spectroscopy (UV‐DRS), Scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT‐IR), and X‐ray photoelectron spectroscopy (XPS) techniques. The catalytic activity of Fe TCPP/mesp‐CTS for ethylbenzene oxidation was investigated and it was proved to be a better catalyst than Fe TCPP/macp‐CTS based on the ethylbenzene conversion, turnover numbers(TON), and the reusability. These results are attributed to the mesocavity and CRC of amino group in Fe TCPP/mesp‐CTS. The highest ethylbenzene conversion and yields of ketone and alcohol were 24.4% and 18.2%, respectively. 相似文献
997.
New designed DNA light switch Ruthenium complexes as DNA photocleavers and Topoisomerase I inhibitors 下载免费PDF全文
Xue‐Wen Liu Yang Xiao Wei‐Gen Peng Li‐Jin Zhao You‐Ming Shen Song‐Bai Zhang Ji‐Lin Lu 《应用有机金属化学》2018,32(4)
Two ruthenium complexes containing a new ligand phipz (phipz = 2‐(1,10‐phenanthroline)‐1H‐imidazo[4,5‐b]phenazine) were designed and synthesized. These complexes were found to inhibit the DNA supercoiled relaxation mediated by topoisomerase I (topo I), cleave DNA under irradiation and bind to calf thymus DNA through intercalative mode. Furthermore, complex 2 shows higher photocleavage activity, topo I inhibition activity and DNA affinity than complex 1 . Additionally, introduction of phenazine unit may be the reason that two complexes exhibit DNA ‘light switch’ behavior. The present work shows that two complexes might be potential as new DNA ‘light switches’, DNA photocleavers and topo I inhibitors. 相似文献
998.
LDH/Tris/Pd (CaAl‐layered double hydroxide/tris (hydroxymethyl)aminomethane/palladium) was synthesized and appraised for its catalytic activity towards the degradation of two selected azo dyes. The decolorization of azo dyes, acid red 18 (AR 18) and reactive yellow 15 (RY 15), requires considerably small amounts of synthesized catalyst. Kinetic studies show that the catalytic decolorization of these azo dyes follows the first order kinetic model. The reported method is simple and applicable; in addition, the stable catalyst can efficiently decolorize model azo dyes with good recyclability. Therefore, LDH/Tris/Pd can be accepted as the possible component for the utilization in wastewater treatment. 相似文献
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