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排序方式: 共有79条查询结果,搜索用时 281 毫秒
31.
Patrick Chène Joëlle Rudloff Joseph Schoepfer Pascal Furet Peter Meier Zhiyan Qian Jean-Marc Schlaeppi Rita Schmitz Thomas Radimerski 《BMC chemical biology》2009,9(1):1-16
Background
Topoisomerase II poisons are in clinical use as anti-cancer therapy for decades and work by stabilizing the enzyme-induced DNA breaks. In contrast, catalytic inhibitors block the enzyme before DNA scission. Although several catalytic inhibitors of topoisomerase II have been described, preclinical concepts for exploiting their anti-proliferative activity based on molecular characteristics of the tumor cell have only recently started to emerge. Topoisomerase II is an ATPase and uses the energy derived from ATP hydrolysis to orchestrate the movement of the DNA double strands along the enzyme. Thus, interfering with ATPase function with low molecular weight inhibitors that target the nucleotide binding pocket should profoundly affect cells that are committed to undergo mitosis.Results
Here we describe the discovery and characterization of a novel purine diamine analogue as a potent ATP-competitive catalytic inhibitor of topoisomerase II. Quinoline aminopurine compound 1 (QAP 1) inhibited topoisomerase II ATPase activity and decatenation reaction at sub-micromolar concentrations, targeted both topoisomerase II alpha and beta in cell free assays and, using a quantitative cell-based assay and a chromosome segregation assay, displayed catalytic enzyme inhibition in cells. In agreement with recent hypothesis, we show that BRCA1 mutant breast cancer cells have increased sensitivity to QAP 1.Conclusion
The results obtained with QAP 1 demonstrate that potent and selective catalytic inhibition of human topoisomerase II function with an ATP-competitive inhibitor is feasible. Our data suggest that further drug discovery efforts on ATP-competitive catalytic inhibitors are warranted and that such drugs could potentially be developed as anti-cancer therapy for tumors that bear the appropriate combination of molecular alterations. 相似文献32.
Synthesis and characterization of single-crystal Ce(OH)CO3 and CeO2 triangular microplates 总被引:1,自引:0,他引:1
Single-crystal cerium hydroxide carbonate (Ce(OH)CO3) triangular microplates with the hexagonal phase have been successfully synthesized by a hydrothermal method at 150 degrees C using cerium nitrate (Ce(NO3)3.6H2O) as the cerium source, aqueous carbamide as both an alkaline and carbon source, and cetyltrimethylammonium bromide (CTAB) as a surfactant. Single-crystal ceria (CeO2) triangular microplates have been fabricated by a thermal decomposition-oxidation process at 650 degrees C for 7 h using single-crystal Ce(OH)CO3 microplates as the precursor. The shape of the Ce(OH)CO3 microplate was sustained after thermal decomposition-oxidation to CeO2. The products were characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), field-emission scanning electron microscopy (FE-SEM), differential scanning calorimetric analysis (DSC), and thermogravimetric analysis (TG). 相似文献
33.
Zhiyan Song Kari J. Parker Idorenyin Enoh Hua Zhao Olarongbe Olubajo 《Magnetic resonance in chemistry : MRC》2010,48(2):123-128
Interaction of polyamines with nucleotides plays a key role in many biological processes. Here we use multiple NMR techniques to characterize interaction of spermidine with adenosine 5′‐triphosphate (ATP). Two‐dimensional 1H‐15N spectra obtained from gs‐HMBC experiments at varied pH show significant shift of N‐1 peak around pH 2.0–7.0 range, suggesting that spermidine binds to N‐1 site of ATP base. The binding facilitates N‐1 deprotonation, shifting its pKa from 4.3 to 3.4. By correlating 15N and 31P chemical shift data, it is clear that spermidine is capable of concurrently binding to ATP base and phosphate sites around pH 4.0–7.0. The self‐diffusion constants derived from 1H PFG‐diffusion measurements provide evidence that binding of spermidine to ATP is in 1:1 ratio, and pH variations do not induce significant nucleotide self‐association in our samples. 31P spectral analysis suggests that at neutral pH, Mg2+ ion competes with spermidine and shows stronger binding to ATP phosphates. From 31P kinetic measurements of myosin‐catalyzed ATP hydrolysis, it is found that binding of spermidine affects the stability and reactivity of ATP. These NMR results are important for advancing the studies on nucleotide–polyamine interaction and its impact on nucleotide structures and activities under varied conditions. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
34.
Porous palladium nanostructures were prepared on a copper sheet previously fixed over the plasma high-temperature area by H2+He arc plasma method. However, dispersed palladium nanoparticles with diameters in 50–90 nm were obtained on the inner wall of vacuum chamber. SEM, TEM, EDXA, XRD and BET were employed to characterize the palladium porous materials. SEM images show that porous palladium nanostructures are composed of spherical particles with diameters of 35 ± 3 nm. This special structure with large surface to volume ratio can be recycled easily for application in the field of catalysis. 相似文献
35.
Li Li Xinrui Hao Hua Chen Liyuan Wang Aolei Chen Xiaotian Song Zhiyan Hu Ying Su Han Lin Pei Fan 《Biomedical chromatography : BMC》2020,34(9):e4897
Asthenozoospermia (AS) is a common factor of male infertility, and its pathogenesis remains unclear. The purpose of this study was to investigate the differential seminal plasma metabolic pattern in asthenozoospermic men and to identify potential biomarkers in relation to spermatogenic dysfunction using sensitive ultra-high-performance liquid chromatography–tandem quadruple time-of-flight MS (UHPLC–Q-TOF/MS). The samples of seminal plasma from patients with AS (n = 20) and healthy controls (n = 20) were checked and differentiated by UHPLC–Q-TOF/MS. Compared with the control group, the AS group showed a total of nine significantly different metabolites, including increases in creatinine, uric acid, N6-methyladenosine (m6A), uridine, and taurine and decreases in carnitine, nicotinamide, N-acetylputrescine and l -palmitoylcarnitine. By analyzing the correlation among these metabolites and clinical computer-assisted semen analysis reports, we found that m6A is significantly correlated with not only the four decreased metabolites but also with sperm count, motility, and curvilinear velocity. Furthermore, nicotinamide was shown to correlate with other identified metabolites, indicating its important role in the metabolic pathway of AS. Current results implied that sensitive untargeted seminal plasma metabolomics could identify distinct metabolic patterns of AS and would help clinicians by offering novel cues for discovering the pathogenesis of male infertility. 相似文献
36.
In this paper, we construct linearly stable quasi-periodic breathers for the Hamiltonian systems in the form \({{\rm i} \dot{q}_n+v_n q_n+\delta|q_n|^2q_n+\varepsilon_n \left(q_{n+1}+q_{n-1} \right)=0,\quad n \in \mathbb{Z}}\) where \({\{v_n\}_{n \in \mathbb{Z}}}\) is a family of time independent identically distributed (i.i.d) random variables with common distribution \({g = dv_n, v_n \in [0,1]}\) and \({|\varepsilon_n| \leq \varepsilon e^{-\varrho |n|}}\) with \({\varepsilon,\varrho > 0}\) . We prove that for \({\varepsilon, \delta}\) sufficiently small, the equation admits a family of small-amplitude and linearly stable, time quasi-periodic solutions for most of the parameters \({\{v_n\}_{n \in \mathbb{Z}}}\) . 相似文献
37.
Facile synthesis of multi‐branched gold nanostructures by using the tetrabutyl ammonium bromide (TBAB) as a capping agent is described. The reaction is carried out in a one‐step process at mild temperature. Gold nanostructures with more than six sharp branches ranging from 70 to 130 nm in length are synthesized in high yield. It is proposed that the relative weak adsorption capacity of TBAB leads to the incompletely covered gold surface and the growth of nanoparticles occurs on the uncovered gold surface, and therefore short branches appear consequently. Then positively charged TBAB layers on the gold surfaces prevent the branches from aggregating with each other which stimulates the branch growth. The prepared branched gold nanoparticles show efficient surface‐enhanced Raman scattering (SERS) properties. Low temperature (4°C) is unfavorable to the formation of multi‐branched gold nanostructures, and only thin small irregular plate‐like nanoparticles are produced. The addition of SDS in TBAB aqueous solution results in forming SDS micelles at much lower concentration of SDS (0.4 mmol/L) as compared to that in pure water, and short branched gold nanoparticles are obtained in the SDS‐TBAB system. 相似文献
38.
In this paper, we prove a new central
limit theorem for nonhomogeneous Markov chain by using the
martingale central limit theorem under the condition of convergence
of transition probability matrices for nonhomogeneous Markov chain
in Cesaro sense, which can not be implied by Dobrushin's work. 相似文献
39.
CHO cells possess easily identifiable karyotypes, and CHO cell chromosomes are large and few in number, making these cells ideal for mutational and drug toxicity studies and suitable for investigations of animal chromosome structure. Here, we used atomic force microscopy (AFM) in the tapping mode for detailed visualizations of Chinese hamster ovary (CHO) cell chromosomes during various mitotic phases, including typical prophase, prometaphase, metaphase, anaphase and telophase. Based on our detailed observations, we were able to divide metaphase and anaphase into sub-phases: metaphase I, II and III, and anaphase I and II. Furthermore, we used the AFM error-signal mode to visualize chromosomal ultrastructures and cytokinesis. While these visualizations were all successful, we found that the image quality was affected by cellular debris, contamination. Collectively, our results show that the AFM technique has great potential for the detailed study of chromosomes and chromosomal ultrastructures during all phases of the cell cycle, but that careful standards of sample preparation must be maintained. 相似文献
40.
设$V\cup_SW$是一个闭的三维流形亏格为$g$的, 弱可约的Heegaard分解, 并且在合痕意义下只有有限组位于曲面不同侧的不相交的压缩圆片, 则它存在一个广义的Heegaard分解: $V\cup_SW=(V_1\cup_{S_1}W_1)\cup_F(W_2\cup_{S_2}V_2)$, 并且满足对于每个$i=1,2$, 压缩体$W_i$都只有一个分离的压缩圆片且$d(S_i)\geq 2$. 进一步的, 如果有有限且多于1组不相交的压缩圆片, 则至少一个$d(S_i)$等于2, 并且Heegaard曲面满足临界性质. 相似文献