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排序方式: 共有313条查询结果,搜索用时 453 毫秒
1.
Dr. Katie R. Witkin Dr. Nicholas R. Vance Colleen Caldwell Dr. Quinn Li Dr. Liping Yu Prof. M. Ashley Spies 《ChemMedChem》2020,15(4):376-384
Glutamate racemases (GR) are members of the family of bacterial enzymes known as cofactor-independent racemases and epimerases and catalyze the stereoinversion of glutamate. D-amino acids are universally important for the proper construction of viable bacterial cell walls, and thus have been repeatedly validated as attractive targets for novel antimicrobial drug design. Significant aspects of the mechanism of this challenging stereoinversion remain unknown. The current study employs a combination of MD and QM/MM computational approaches to show that the GR from H. pylori must proceed via a pre-activation step, which is dependent on the enzyme's flexibility. This mechanism is starkly different from previously proposed mechanisms. These findings have immediate pharmaceutical relevance, as the H. pylori GR enzyme is a very attractive allosteric drug target. The results presented in this study offer a distinctly novel understanding of how AstraZeneca's lead series of inhibitors cripple the H. pylori GR's native motions, via prevention of this critical chemical pre-activation step. Our experimental studies, using SPR, fluorescence and NMR WaterLOGSY, show that H. pylori GR is not inhibited by the uncompetitive mechanism originally put forward by Lundqvist et al.. The current study supports a deep connection between native enzyme motions and chemical reactivity, which has strong relevance to the field of allosteric drug discovery. 相似文献
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In this study, static and fatigue tests were conducted using coach-peel, cross-tension and tensile–shear specimens with Al-5052 plates for evaluation of the fatigue strength of the SPR joints. For the coach-peel, cross-tension and tensile–shear geometries, the ratios of the fatigue endurance limit to static strength were 11%, 14% and 34%, respectively, assuming fatigue cycles of 106 for an infinite lifetime. The equivalent stress intensity factor range can properly predict the current experimental fatigue lifetime. Fatigue crack initiation occurred due to fretting damage between the upper and lower sheets and between the rivet and these sheets. 相似文献
3.
Hongxia Chen Feng Liu Fangjie Qi Kwangnak Koh Keming Wang 《International journal of molecular sciences》2014,15(4):5496-5507
Three calix[4]arene (Cal-4) derivatives which separately contain ethylester (1), carboxylic acid (2), and crownether (3) at the lower rim with a common reactive thiol at the upper rim were synthesized and constructed to self-assembled monolayers (SAMs) on Au films. After spectroscopic characterization of the monolayers, surface coverage and orientation of antibody immobilized on the Cal-4 derivative SAMs were studied by surface plasmon resonance (SPR) technique. Experimental results revealed that the antibody could be immobilized on the Cal-4 derivatives spontaneously. The orientation of absorbed antibody on the Cal-4 derivative SAMs is related to the SAM’s dipole moment. The possible orientations of the antibody immobilized on the Cal-4 derivative 1 SAM are lying-on or side-on, while on the Cal-4 derivative 2 and Cal-4 derivative 3 head-on and end-on respectively. These experimental results demonstrate the surface dipole moment of Cal-4 derivative appears to be an important factor to antibody orientation. Cal-4 derivatives are useful in developing site direct protein chips. 相似文献
4.
This work develops a highly sensitive immunoassay sensor for use in graphene oxide sheet (GOS)-based surface plasmon resonance (SPR) chips. This sensing film, which is formed by chemically modifying a GOS surface, has covalent bonds that strongly interact with the bovine serum albumin (BSA), explaining why it has a higher sensitivity. This GOS film-based SPR chip has a BSA concentration detection limit that is 100 times higher than that of the conventional Au-film-based sensor. The affinity constants (KA) on the GOS film-based SPR chip and the conventional SPR chip for 100 μg/ml BSA are 80.82 × 106 M-1 and 15.67 × 106 M-1, respectively. Therefore, the affinity constant of the GOS film-based SPR chip is 5.2 times higher than that of the conventional chip. With respect to the protein-protein interaction, the SPR sensor capability to detect angle changes at a low concentration anti-BSA of 75.75 nM on the GOS film-based SPR chip and the conventional SPR chip is 36.1867 and 26.1759 mdeg, respectively. At a high concentration, anti-BSA of 378.78 nM on the GOS film-based SPR chip and the conventional SPR chip reveals two times increases in the SPR angle shift. Above results demonstrate that the GOS film is promising for highly sensitive clinical diagnostic applications. 相似文献
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光纤表面等离子体共振(SPR)传感器是目前应用在环境介质检测和生物大分子检测等方面的新型、高精度传感器。首先,以表面等离子体共振传感理论为基础,对系统检测结果进行数据处理,得出采用均值估计的线性模型。在不同时刻与相同环境介质下,检测某一溶液的十组光谱数据并进行均值估计,从而得到有效的共振波长。其次,利用小波分析方法进行信号处理,校正了噪声产生的漂移,对光谱信号压缩处理,以提高检测精度。再通过Matlab进行模拟仿真优化传感系统性能。并对不同折射率溶液如蒸馏水、酒精等进行检测,得到了良好的光谱响应曲线,证明了在检测范围内折射率和共振波长之间具有良好的线性关系。 相似文献
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Edy Wijaya Cédric Lenaerts Sophie Maricot Juriy Hastanin Serge Habraken Jean-Pierre Vilcot Rabah Boukherroub Sabine Szunerits 《Current Opinion in Solid State & Materials Science》2011,15(5):208-224
Surface plasmon resonance (SPR)-based biosensors are very powerful tools for the study of biomolecular interactions, chemical detection and immunoassays. This paper reviews the performance of various SPR structures and detection schemes focusing on propagating surface plasmons generated in planar structures. Some aspects of their surface functionalization, the key element which imparts biofunctionality to these structures and hence transforming them into biosensors, will also be discussed accordingly. The ultimate performance of SPR-based biosensors will thus be determined by both their inherent optical performance and suitable surface functionalization. 相似文献
9.
分子印迹膜SPR传感器检测氯磺隆的方法 总被引:1,自引:0,他引:1
研究使用了中国科学院电子学研究所自行研制的高灵敏度单通道SPR分析仪和进样装置,仪器为棱镜耦合型SPR传感器结构,其检测角度范围是40°~70°,折射率检测范围为1.04~1.47,谐振角的精度在0.001°。适用于SPR分析仪的分子印迹芯片采用PVC-MIP共聚膜法制备,SPR角度扫描结果表明,200nm以下厚度芯片具有较好的SPR吸收特性。以氯磺隆为模板的分子印迹膜与不加氯磺隆的分子印迹膜对比实验发现前者具有特异性结合的能力。实验对浓度0.1,0.2,0.5和1μg/mL的氯磺隆进行了SPR定点检测,这四种浓度氯磺隆的折射率响应信号满足线性关系,相关系数R=0.996 4。实验中对低浓度的氯磺隆进行反复检测,检测到50ng/mL的氯磺隆,满足农残检测的要求。 相似文献
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