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61.
USING CELL-FRACTIONATION AND PHOTOCHEMICAL CROSSLINKING METHODS TO DETERMINE THE CELLULAR BINDING SITE(S) OF THE ANTITUMOR DRUG DMP 840 总被引:1,自引:0,他引:1
Abstract— In order to understand its mechanism of action we have begun an effort to better define the cellular target of action of the experimental antitumor agent DMP 840 (NSC D640430; (R, R)-2,2'-(1,2-ethanediylbis(imino-(1 -methyl-2,1 -ethanediyl)))-bis(5-nitro-1 H-benz(de)isoquinoline-1,3-(2H)-dione) dimethanesulfonate). Using a combination of gentle cell fractionation procedures and a previously unidentified photochemical crosslinking reaction, we have shown that after the drug is added to cultured Clone A cells, more than 80% of the drug that is found associated with cells partitions to the chromatin-containing structural framework of the cell and that the primary target after crosslinking with 360 nm light is DNA. While DMP 840 photoreacts quite efficiently with purified RNA in vitro , no photoat-tachment of the drug to RNA was observed in cells. In vitro photochemical studies also reveal that while GC-rich DNA is a preferred target for drug interaction, AT-rich DNA is more active in the photochemical crosslinking reaction. These results suggest that DMP 840 probably kills cells by interfering with DNA-metabolic processes, and that the drug and its derivatives are likely to be useful photoactive molecular probes for investigating higher order chromatin structures in cells. 相似文献
62.
Nat Jack 《The Journal of the Operational Research Society》1991,42(9):759-766
In this paper an integral equation approach is given for evaluating the expected cost of repair replacement policies over finite time horizons. An asymptotic estimate of this expected cost is also obtained. The policy involving imperfect repair on failure with replacement after N failures is taken as an illustrative example and optimal policies N* are found for both infinite and finite time horizons of use. 相似文献
63.
M. Natália D. S. Cordeiro Roberto Cammi José A. N. F. Gomes Jacopo Tomasi 《Theoretical chemistry accounts》1992,82(3-4):165-187
The interaction energyE of the systems Cu+-H2O and Cl–-H2O has been computed over a wide range of distances and orientations with the MINI-1 basis set in the SCF approximation. The interaction energy has been decomposed according to the Kitaura-Morokuma scheme, with and without counterpoise (CP) corrections to the basis set superposition error. The importance of this correction is analysed by its effect upon Monte Carlo calculations of the Cu+-water and Cl–-water systems, using two-body potentials without and with CP corrections. The effect of CP corrections on theE analysis is similar to that found in other systems of analogous composition (of the general type ion plus neutral ligands), but with significant differences in the details. The effect of the CP corrections to the interaction potential, and then on the results of the Monte Carlo simulations, is small for the Cu+ ion, but remarkable for the Cl– ion. 相似文献
64.
Natália Martins Delfim F. M. Torres 《Journal of Optimization Theory and Applications》2012,155(2):453-476
We obtain Euler?CLagrange and transversality optimality conditions for higher-order infinite horizon variational problems on a time scale. The new necessary optimality conditions improve the classical results both in the continuous and discrete settings: Our results seem new and interesting even in the particular cases when the time scale is the set of real numbers or the set of integers. 相似文献
65.
66.
Natália Akemi Kohori Martin Kássio Leme da Silva Ivana Cesarino 《Journal of Solid State Electrochemistry》2018,22(1):141-148
Bioelectrodes were developed based on a simple deposition of graphene oxide (GO) or reduced graphed oxide (rGO) and laccase (Lac) on a glassy carbon (GC) electrode surface. The morphology and electrochemical behavior of the biosensors were characterized by scanning electron microscopy and cyclic voltammetry. These results demonstrated that only rGO was successfully applied for the immobilization of the laccase enzyme, improving the analytical signal for the determination of dopamine. The GC/rGO/Lac biosensor was applied to the detection of dopamine in synthetic urine and plasmatic serum samples, achieving a detection limit of 91.0 nmol L?1. 相似文献
67.
Milla Alves Baffi Natália Martin Thaise Mariá Tobal Ana Lúcia Ferrarezi João Henrique Ghilardi Lago Maurício Boscolo Eleni Gomes Roberto Da-Silva 《Applied biochemistry and biotechnology》2013,171(7):1681-1691
An extracellular ethanol-tolerant β-glucosidase from Sporidiobolus pararoseus was purified to homogeneity and characterized, and its potential use for the enhancement of wine aroma was investigated. The crude enzymatic extract was purified in four steps (concentration, dialysis, ultrafiltration, and chromatography) with a yield of around 40 % for total activity. The purified enzyme (designated Sp-βgl-P) showed a specific activity of approximately 20.0 U/mg, an estimated molecular mass of 63 kDa after sodium dodecyl sulfate polyacrylamide gel electrophoresis, and isoelectric point of 5.0 by isoelectric focusing. Sp-βgl-P has optimal activity at pH 4.0 and at 55 °C. It was stable in a broad pH range at low temperatures and it was tolerant to ethanol and glucose, indicating suitable properties for winemaking. The hydrolysis of glycosidic terpenes was analyzed by adding Sp-βgl-P directly to the wines. The released terpene compounds were evaluated by gas chromatography/mass spectrometry. The enzymatic treatment significantly increased the amount of free terpenes, suggesting that this enzyme could potentially be applicable in wine aroma improvement. 相似文献
68.
Márcio G. dos Santos Felipe S. Moreno Akila L. de Oliveira Isadora C. F. Oliveira Natália Tribuiani José C. Cogo 《Natural product research》2019,33(16):2389-2393
Galactia glaucescens leaves are popularly used against snakebites in Brazil. The hydroethanolic extract from aerial parts of G. glaucescens (HEGg) was assayed against the neurotoxicity and myotoxicity induced by Bothrops jararacussu venom. A traditional myographic technique was applied for neurotoxicity and the resulting muscles were treated routinely by light microscopy analysis for myotoxicity. Additionally, the antimicrobial potential of HEGg was evaluated against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa strains, as well as Rutin was isolated for the first time in this specie using chromatographic and spectroscopic methods and its antiophidian property was assessed. HEGg totally prevents the neurotoxicity and myotoxicity effects caused by B. jararacussu, but did not show any antimicrobial effect. Concluding, HEGg and Rutin were able to counteract the toxic effects of the venom and confirmed the antiophidian potential, but not antimicrobial, of G. glaucescens as an alternative for neutralization of B. jararacussu venom. 相似文献
69.
70.
Ming-Tsz Chen Bing-Yan Hsieh Yi-Hung Liu Kuo-Hui Wu Natália Lussari Ataualpa A.C. Braga 《应用有机金属化学》2020,34(10):e5870
This work examines how N-donor bridged spacer ligands affect N-heterocyclic carbene (NHC) palladium complexes catalytic activities for Suzuki coupling reaction. Different degrees of structural flexibility binuclear NHC palladium complexes were synthesized. The more flexible nitrogen-based alkyl chain ligand shows similar performance with cycloamine counterparts in the Suzuki coupling reaction. Suzuki coupling examples were used in air and ambient temperature to reach moderate to completion yields in short time. Density functional theory calculations showed that the chelate effect, associated with a single Pd complex mechanism, plays a fundamental role in the pre-catalysis stage, supporting a reasonable of the kinetic activity observed experimentally. 相似文献