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排序方式: 共有151条查询结果,搜索用时 15 毫秒
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Sardarian A Douglas KT Read M Sims PF Hyde JE Chitnumsub P Sirawaraporn R Sirawaraporn W 《Organic & biomolecular chemistry》2003,1(6):960-964
Pyrimethamine acts against malarial parasites by selectively inhibiting their dihydrofolate reductase-thymidylate synthase. Resistance to pyrimethamine in Plasmodium falciparum is due to point mutations in the DHFR domain, initially at residue 108 (S108N), with additional mutations imparting much greater resistance. Our previous work, the development of a simple rational drug design strategy to overcome such resistance, used suitable meta-substituents in the pyrimethamine framework to avoid the unfavorable steric clash with mutant side chains at position 108. Interestingly, the meta-chloro analog of pyrimethamine not only overcame the resistance due to S108N, but also that contributed by the more remote mutation, C59R. The present work improves on this by means of other meta-substituents. Against wild type DHFR, double mutant types A16V + S108T and C59R + S108T, and the highly pyrimethamine/cycloguanil-resistant quadruple-mutant form N51I + C59R + S108N + I164L, pyrimethamine itself gave Ki values of 1.5, 2.4, 72.3 and 859 nM, respectively. The meta-substituted analogs, especially the meta-bromo analog, were much more powerful inhibitors of these DHFRs, including the quadruple-mutant form (meta-bromo analog, Ki 5.1 nM). For comparison, the dihydropyrazine antifolate, WR99210, gave Ki values of 0.9, 3.2, 0.8 and 0.9 nM, respectively. Ki values were also measured against recombinant human DHFR, as were their activities against the growth of Plasmodium falciparum cultures bearing the double mutations (FCB and K1 strains) and quadruple mutation (V1/S) and the wild type (3D7). The meta-analogs were highly active against all of these, with the meta-bromo again being the strongest, having an IC50 of 37 nM against V1/S, compared to > 5000 nM for pyrimethamine itself and 1.1 nM for WR99210. 相似文献
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Plasma Thermal Conversion of Methane to Acetylene 总被引:2,自引:0,他引:2
Fincke J. R. Anderson R. P. Hyde T. Detering B. A. Wright R. Bewley R. L. Haggard D. C. Swank W. D. 《Plasma Chemistry and Plasma Processing》2002,22(1):107-138
This paper describes a re-examination of a known process for the direct plasma thermal conversion of methane to acetylene. Conversion efficiencies (% methane converted) approached 100% and acetylene yields in the 90–95% range with 2–4% solid carbon production were demonstrated. Specificity for acetylene was higher than in prior work. Improvements in conversion efficiency, yield, and specificity were due primarily to improved injector design and reactant mixing, and minimization of temperature gradients and cold boundary layers. At the 60-kilowatt scale cooling by wall heat transfer appears to be sufficient to quench the product stream and prevent further reaction of acetylene resulting in the formation of heavier hydrocarbon products or solid carbon. Significantly increasing the quenching rate by aerodynamic expansion of the products through a converging–diverging nozzle led to a reduction in the yield of ethylene but had little effect on the yield of other hydrocarbon products. While greater product selectivity for acetylene has been demonstrated, the specific energy consumption per unit mass of acetylene produced was not improved upon. A kinetic model that includes the reaction mechanisms resulting in the formation of acetylene and heavier hydrocarbons, through benzene, is described. 相似文献
4.
T-2 toxin and diacetoxyscirpenol (DAS), two trichothecene mycotoxins containing one hydroxy group, have been volatilized by induction heating, revolatilized, and analyzed by gas chromatography (GC) and/or GC mass spectroscopy. Seventy to eighty percent of DAS was recovered by this system; 60–70% T-2 toxin was recovered. When the hydroxy group is derivatized by acetate, 90–100% recovery is obtained. Other trichothecenes of the macrocyclic ester type (e.g., Roridan A) were also tried. Ten to twenty percent of the macrocyclic ester was obtained without derivatization. 相似文献
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Sanford TW Allshouse GO Marder BM Nash TJ Mock RC Spielman RB Seamen JF McGurn JS Jobe D Gilliland TL Vargas M Struve KW Stygar WA Douglas MR Matzen MK Hammer JH De Groot JS Eddleman JL Peterson DL Mosher D Whitney KG Thornhill JW Pulsifer PE Apruzese JP Maron Y 《Physical review letters》1996,77(25):5063-5066
7.
Banks CE Kruusma J Hyde ME Salimi A Compton RG 《Analytical and bioanalytical chemistry》2004,379(2):277-282
Bismuth-modified glassy carbon electrodes have been investigated for their suitability in sonoelectroanalysis. The stability of the bismuth film to the application of ultrasound was assessed via voltammetric and atomic force microscopy (AFM) studies which revealed little ablation at powers up to an intensity of 130 W cm–2 delivered from a 25-kHz sonic horn. Furthermore, bismuth-film-modified glassy carbon electrodes were evaluated for the sonoelectroanalytical quantification of zinc and cadmium. Detection limits of 2×10–7 M and 6×10–9 M respectively were found after a 60-s deposition time via an acoustically assisted deposition protocol. 相似文献
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Iodice M Cusanno F Acha A Ambrozewicz P Aniol KA Baturin P Bertin PY Benaoum H Blomqvist KI Boeglin WU Breuer H Brindza P Bydzovský P Camsonne A Chang CC Chen JP Choi S Chudakov EA Cisbani E Colilli S Coman L Craver BJ De Cataldo G de Jager CW De Leo R Deur AP Ferdi C Feuerbach RJ Folts E Fratoni R Frullani S Garibaldi F Gayou O Giulani F Gomez J Gricia M Hansen JO Hayes D Higinbotham DW Holmstrom TK Hyde CE Ibrahim HF Jiang X Kaufman LJ Kino K Kross B Lagamba L LeRose JJ Lindgren RA 《Physical review letters》2007,99(5):052501
An experiment measuring electroproduction of hypernuclei has been performed in hall A at Jefferson Lab on a 12C target. In order to increase counting rates and provide unambiguous kaon identification two superconducting septum magnets and a ring imaging Cherenkov detector were added to the hall A standard equipment. An unprecedented energy resolution of less than 700 keV FWHM has been achieved. Thus, the observed (Lambda)(12)B spectrum shows for the first time identifiable strength in the core-excited region between the ground-state s-wave Lambda peak and the 11 MeV p-wave Lambda peak. 相似文献
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