排序方式: 共有36条查询结果,搜索用时 15 毫秒
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Terephthalamide derivatives as mimetics of helical peptides: disruption of the Bcl-x(L)/Bak interaction 总被引:4,自引:0,他引:4
Yin H Lee GI Sedey KA Rodriguez JM Wang HG Sebti SM Hamilton AD 《Journal of the American Chemical Society》2005,127(15):5463-5468
A series of Bcl-x(L)/Bak antagonists, based on a terephthalamide scaffold, was designed to mimic the alpha-helical region of the Bak peptide. These molecules showed favorable in vitro activities in disrupting the Bcl-x(L)/Bak BH3 domain complex (terephthalamides 9 and 26, K(i) = 0.78 +/- 0.07 and 1.85 +/- 0.32 microM, respectively). Extensive structure-affinity studies demonstrated a correlation between the ability of terephthalamide derivatives to disrupt Bcl-x(L)/Bak complex formation and the size of variable side chains on these molecules. Treatment of human HEK293 cells with the terephthalamide derivative 26 resulted in disruption of the Bcl-x(L)/Bax interaction in whole cells with an IC(50) of 35.0 microM. Computational docking simulations and NMR experiments suggested that the binding cleft for the BH3 domain of the Bak peptide on the surface of Bcl-x(L) is the target area for these synthetic inhibitors. 相似文献
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Ahmed Alsaedi Mohammed S. Alhothuali Bashir Ahmad Sebti Kerbal Mokhtar Kirane 《Mathematical Methods in the Applied Sciences》2014,37(13):2009-2016
Sobolev type nonlinear equations with time fractional derivatives are considered. Using the test function method, limiting exponents for nonexistence of solutions are found. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
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The effects of surface waviness (λ?=?0, 0.125, 0.25, 0.5) and nanoparticle dispersion (??=?0, 0.05, 0.1) on solidification of Cu-water nanofluid inside a vertical enclosure are investigated numerically for different Grashof number (Gr?=?105, 106, 107). An enthalpy porosity technique is used to trace the solid and liquid interface. Comparisons with previously published works show the accuracy of the obtained results. A maximum of 25.9% relative variation of freezing time with surface waviness was observed for λ?=?0.5, while the relative variation of freezing time with nanoparticles in comparison with surface waviness was negative for high values of λ. It was observed that surface waviness can be used to control the solidification time based on enhancing different mechanism of solidification. 相似文献
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The reaction of cesium fluoride with the 2-acyloxy 3-chloro 2-chloromethylpropanamides () gave the 3-acyloxy 3-chloromethyl azetidine 2-ones () . Treated by powdered potassium hydroxide, and were converted into the 1-oxa 4-oxo 5-aza spiro (2,3) hexanes. These reactions in heterogeneous media were very selective and gave excellent yields. 相似文献
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Machida S Usuba K Blaskovich MA Yano A Harada K Sebti SM Kato N Ohkanda J 《Chemistry (Weinheim an der Bergstrasse, Germany)》2008,14(5):1392-1401
Synthetic chemical probes designed to simultaneously targeting multiple sites of protein surfaces are of interest owing to their potential application as site specific modulators of protein-protein interactions. A new approach toward bivalent inhibitors of mammalian type I geranylgeranyltransferase (GGTase I) based on module assembly for simultaneous recognition of both interior and exterior protein surfaces is reported. The inhibitors synthesized in this study consist of two modules linked by an alkyl spacer; one is the tetrapeptide CVIL module for binding to the interior protein surface (active pocket) and the other is a 3,4,5-alkoxy substituted benzoyl motif that contains three aminoalkyl groups designed to bind to the negatively charged protein exterior surface near the active site. The compounds were screened by two distinct enzyme inhibition assays based on fluorescence spectroscopy and incorporation of a [(3)H]-labeled prenyl group onto a protein substrate. The bivalent inhibitors block GGTase I enzymatic activity with K(i) values in the submicromolar range and are approximately one order of magnitude and more than 150 times more effective than the tetrapeptide CVIL and the methyl benzoate derivatives, respectively. The bivalent compounds 6 and 8 were shown to be competitive inhibitors, suggesting that the CVIL module anchors the whole molecule to the GGTase I active site and delivers the other module to the targeting protein surface. Thus, our module-assembly approach resulted in simultaneous multiple-site recognition, and as a consequence, synergetic inhibition of GGTase I activity, thereby providing a new approach in designing protein-surface-directed inhibitors for targeting protein-protein interactions. 相似文献
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B. Amimour M. Slimani C. Sifi R. Khémissi H. Meradji S. Ghemid S. Bin Omran R. Khenata 《Chinese Journal of Physics (Taipei)》2017,55(2):367-377
In this work, the full-potential linearized augmented plane wave (FP-LAPW) method was used to calculate the structural, electronic, thermal and thermodynamic properties of BaS and CaS compounds and their ternary mixtures, Ba1?xCaxS. The local-density approximation (LDA), the Wu-Cohen generalized gradient approximation (WC-GGA) and the Perdew-Burke-Ernzerhof generalized gradient approximation (PBE-GGA) were used as the exchange-correlation potential. Moreover, the modified Becke–Johnson approximation was also used for the band structure calculations. We examined the composition effect on the lattice constants, bulk modulus and band gap. The microscopic origins of the band gap bowing were characterized in detail using the approach of Zunger and colleagues. Pressure and temperature effects on the lattice parameter, heat capacity, Debye temperature, Grüneisen parameter, and thermal expansion coefficient were predicted using the quasi-harmonic Debye model. The thermodynamic stability of these alloys was investigated by calculating the excess enthalpy of mixing, ?Hm, and the phase diagram. It was shown that these alloys are stable at high temperature. 相似文献
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First-principle calculations on the structural, electronic, optical, elastic and thermal properties of the chalcopyrite \(\hbox {MgXAs}_{2}\) (\(\hbox {X}=\hbox {Si}, \hbox {Ge}\)) have been performed within the density functional theory (DFT) using the full-potential linearized augmented plane wave (FP-LAPW) method. The obtained equilibrium structural parameters are in good agreement with the available experimental data and theoretical results. The calculated band structures reveal a direct energy band gap for the interested compounds. The predicted band gaps using the modified Becke–Johnson (mBJ) exchange approximation are in fairly good agreement with the experimental data. The optical constants such as the dielectric function, refractive index, and the extinction coefficient are calculated and analysed. The independent elastic parameters namely, \(C_{11}\), \(C_{12}\), \(C_{13}\), \(C_{33}\), \(C_{44}\) and \(C_{66 }\) are evaluated. The effects of temperature and pressure on some macroscopic properties of \(\hbox {MgSiAs}_{2}\) and \(\hbox {MgGeAs}_{2}\) are predicted using the quasiharmonic Debye model in which the lattice vibrations are taken into account. 相似文献
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The aim of the present work is the numerical computation of the average magnetic induction in the cross-section of a non-oriented 3% Si-Fe sheet by solving the magnetic diffusion equation. Jiles’ dynamic model is used to describe the magnetization law. The obtained results are compared with those of the measurements carried out for frequencies of 0.5, 50, 200 and 500 Hz. A satisfactory agreement is obtained between both types of results. 相似文献