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171.
Ale Ricka Libor Dostl Roman Jambor Vladimír Buchta Jirí Brus Ivana Císarov Michal Holcapek Jaroslav Holecek 《应用有机金属化学》2002,16(6):315-322
A set of seven [2,6‐bis(dimethylaminomethyl)phenyl]diphenyltin(IV) ({[(CH3)2NCH2]2(C6H3)}(C6H5)2Sn+X?) ionic organotin(IV) compounds (X = Br, NO3, CN, SCN, SeCN, BF4 and PF6) has been prepared and characterized by electrospray ionization mass spectrometry, 1H NMR spectroscopy in CDCl3,119Sn NMR in CDCl3 and DMSO‐d6 solution, as well as by 13C and 119Sn CP/MAS NMR spectroscopy and X‐ray diffraction techniques in the solid state. The in vitro antifungal activity of these water‐soluble ionic organotin(IV) compounds was compared with starting compounds and the antifungal drugs currently in clinical use. Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
172.
Identification of a β1/β2‐Specific Sulfonamide Proteasome Ligand by Crystallographic Screening 下载免费PDF全文
Dr. Philipp Beck Prof. Dr. Michèle Reboud‐Ravaux Prof. Dr. Michael Groll 《Angewandte Chemie (International ed. in English)》2015,54(38):11275-11278
The proteasome represents a validated drug target for the treatment of cancer, however, new types of inhibitors are required to tackle the development of resistant tumors. Current fluorescence‐based screening methods suffer from low sensitivity and are limited to the detection of ligands with conventional binding profiles. In response to these drawbacks, a crystallographic screening procedure for the discovery of agents with a novel mode of action was utilized. The optimized workflow was applied to the screening of a focused set of compounds, resulting in the discovery of a β1/β2‐specific sulfonamide derivative that noncovalently binds between subunits β1 and β2. The binding pocket displays significant differences in size and polarity between the immuno‐ and constitutive proteasome. The identified ligand thus provides valuable insights for the future structure‐based design of subtype‐specific proteasome inhibitors. 相似文献
173.
174.
Dr. Hee‐Sun Han Paul G. Cantalupo Dr. Assaf Rotem Dr. Shelley K. Cockrell Martial Carbonnaux Prof. James M. Pipas Prof. David A. Weitz 《Angewandte Chemie (International ed. in English)》2015,54(47):13985-13988
Metagenomic studies suggest that only a small fraction of the viruses that exist in nature have been identified and studied. Characterization of unknown viral genomes is hindered by the many genomes populating any virus sample. A new method is reported that integrates drop‐based microfluidics and computational analysis to enable the purification of any single viral species from a complex mixed virus sample and the retrieval of complete genome sequences. By using this platform, the genome sequence of a 5243 bp dsDNA virus that was spiked into wastewater was retrieved with greater than 96 % sequence coverage and more than 99.8 % sequence identity. This method holds great potential for virus discovery since it allows enrichment and sequencing of previously undescribed viruses as well as known viruses. 相似文献
175.
Identification strategies for flame retardants employing time‐of‐flight mass spectrometric detectors along with spectral and spectra‐less databases 下载免费PDF全文
Alin C. Ionas Ana Ballesteros Gómez Pim E. G. Leonards Adrian Covaci 《Journal of mass spectrometry : JMS》2015,50(8):1031-1038
In the past, the preferred strategy for the identification of unknown compounds was to search in an appropriate mass spectral database for spectra obtained using either electron ionisation (GC‐MS analyses) or collision‐induced dissociation (LC‐MS/MS analyses). Recently, an increase has been seen in the use of accurate mass instruments and spectra‐less databases, based on monoisotopic accurate mass alone. In this article, we describe a systematic workflow for the screening and identification of new flame retardants. This approach utilises LC‐quadrupole‐time‐of‐flight MS and spectra‐less databases based only on monoisotopic accurate mass for the identification of ‘unknowns’. An in‐house database was built, and the input parameters used in the data analysis process were optimised for flame retardant chemicals, so that it can be easily transferred to other laboratories. The procedure was successfully applied to dust, foam and textiles from car interiors and indoor consumer products. The developed method was demonstrated for the main new flame retardant present in Antiblaze V6 and for the three unreported reaction by‐products/impurities present in the same technical mixture. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
176.
Identification of Structure–Activity Relationships from Screening a Structurally Compact DNA‐Encoded Chemical Library 下载免费PDF全文
Dr. Raphael M. Franzini Dr. Torun Ekblad Dr. Nan Zhong Moreno Wichert Willy Decurtins Angela Nauer Mauro Zimmermann Dr. Florent Samain Dr. Jörg Scheuermann Dr. Peter J. Brown Prof. Dr. Jonathan Hall Dr. Susanne Gräslund Prof. Dr. Herwig Schüler Prof. Dr. Dario Neri 《Angewandte Chemie (International ed. in English)》2015,54(13):3927-3931
Methods for the rapid and inexpensive discovery of hit compounds are essential for pharmaceutical research and DNA‐encoded chemical libraries represent promising tools for this purpose. We here report on the design and synthesis of DAL‐100K, a DNA‐encoded chemical library containing 103 200 structurally compact compounds. Affinity screening experiments and DNA‐sequencing analysis provided ligands with nanomolar affinities to several proteins, including prostate‐specific membrane antigen and tankyrase 1. Correlations of sequence counts with binding affinities and potencies of enzyme inhibition were observed and enabled the identification of structural features critical for activity. These results indicate that libraries of this type represent a useful source of small‐molecule binders for target proteins of pharmaceutical interest and information on structural features important for binding. 相似文献
177.
Dr. Junhe Ma Qing Cao Dr. Sarah M. McLeod Keith Ferguson Ning Gao Prof. Alexander L. Breeze Dr. Jun Hu 《Angewandte Chemie (International ed. in English)》2015,54(16):4764-4767
An NMR‐based approach marries the two traditional screening technologies (phenotypic and target‐based screening) to find compounds inhibiting a specific enzymatic reaction in bacterial cells. Building on a previous study in which it was demonstrated that hydrolytic decomposition of meropenem in living Escherichia coli cells carrying New Delhi metallo‐β‐lactamase subclass 1 (NDM‐1) can be monitored in real time by NMR spectroscopy, we designed a cell‐based NMR screening platform. A strong NDM‐1 inhibitor was identified with cellular IC50 of 0.51 μM , which is over 300‐fold more potent than captopril, a known NDM‐1 inhibitor. This new screening approach has great potential to be applied to targets in other cell types, such as mammalian cells, and to targets that are only stable or functionally competent in the cellular environment. 相似文献
178.
Jun‐Seok Lee Jae Wook Lee Namyoung Kang Hyung‐Ho Ha Young‐Tae Chang 《Chemical record (New York, N.Y.)》2015,15(2):495-510
Synthetic molecules that modulate and probe biological events are critical tools in chemical biology. Utilizing combinatorial and diversity‐oriented synthetic strategies, access to large numbers of small molecules is becoming more and more feasible, and research groups in this field can take advantage of the power of chemical diversity. Since the majority of early studies were focused on the discovery of compounds that perturb protein functions, diversity‐based approaches are often considered as therapeutic lead discovery tactics. However, the diversity‐oriented approach can also be applied to advance distinct aims, such as target protein identification, or the development of imaging probes and sensors. This review provides a personal perspective of the chemical‐diversity‐based approach and how this principle can be adapted to various chemical biology studies. 相似文献
179.
Practical method for the rapid screening of xanthine oxidase inhibitors in herbal extracts by high‐performance liquid chromatography based on on‐line precolumn enzymatic reaction 下载免费PDF全文
Chun‐Hua Zhou De‐Qiang Li Yuan‐Yuan Xiao Xiu‐Ling Yang Zhi‐Qing Zhang 《Journal of separation science》2015,38(13):2267-2271
A high‐performance liquid chromatography method with on‐line precolumn enzymatic reaction for the screening of xanthine oxidase inhibitors in natural extracts was developed. In this method, the enzymatic reaction occurred at the capillary inlet during a predetermined waiting period, after which the reaction product, uric acid, was separated and detected by liquid chromatography using ultraviolet absorption at 295 nm. Enzyme inhibition can be read out directly from the reduced peak area of uric acid in comparison to a reference chromatogram obtained in the absence of any inhibitor. In the present study, the availability of on‐line precolumn enzymatic reaction with ultraviolet detection was firstly evaluated by determining the inhibitory mechanism and IC50 values of allopurinol, a commercially available positive drug. Then, the newly developed method was applied to screening of ten natural extracts from traditional Chinese medicine and as a result, the extract of Epimedium sagittatum (Sieb. et Zucc.) Maxim was found to be most positive for xanthine oxidase inhibition. The results obtained were compared with those obtained by offline enzyme assay and the effectiveness of the present method was confirmed. A rapid, low‐cost, and fully automated method for xanthine oxidase inhibitor screening was proposed. 相似文献
180.
Sabyasachi Kar Yu‐Shu Wang Wei‐Qi Li Xiu‐Dong Sun 《International journal of quantum chemistry》2015,115(22):1573-1579
The effect of plasma screening on the dynamic dipole polarizability (DPP) of two‐electron ions Be2+, B3+, and C4+ has been investigated using highly correlated exponential wave functions within the framework of pseudostate summation technique and Debye screening concept. Plasma‐screening effect on the oscillator strengths (OS) of the ultraviolet and visible series has also been investigated for the systems Li+, Be2+, B3+, C4+. The DPP are reported as functions of screening parameters. The OS for S‐P transitions are also reported for various screening parameters. The OS and dynamic polarizability show interesting behavior with increasing screening strength and nuclear charge. © 2015 Wiley Periodicals, Inc. 相似文献