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排序方式: 共有989条查询结果,搜索用时 15 毫秒
981.
982.
Rafael W. Hartmann Raphael Fahrner Dr. Denys Shevshenko Prof. Mårten Fyrknäs Prof. Rolf Larsson Dr. Fredrik Lehmann Prof. Luke R. Odell 《ChemMedChem》2020,15(24):2500-2512
Auristatins are a class of ultrapotent microtubule inhibitors, whose growing clinical popularity in oncology is based upon their use as payloads in antibody-drug conjugates (ADCs). The most widely utilized auristatin, MMAE, has however been shown to cause apoptosis in non-pathological cells proximal to the tumour (“bystander killing”). Herein, we introduce azastatins, a new class of auristatin derivatives encompassing a side chain amine for antibody conjugation. The synthesis of Cbz-azastatin methyl ester, which included the C2-elongation and diastereoselective reduction of two proteinogenic amino acids as key transformations, was accomplished in 22 steps and 0.76 % overall yield. While Cbz-protected azastatin methyl ester (0.13–3.0 nM) inhibited proliferation more potently than MMAE (0.47–6.5 nM), removal of the Cbz-group yielded dramatically increased IC50-values (9.8–170 nM). We attribute the reduced apparent cytotoxicity of the deprotected azastatin methyl esters to a lack of membrane permeability. These results clearly establish the azastatins as a novel class of cytotoxic payloads ideally suited for use in next-generation ADC development. 相似文献
983.
984.
985.
A.-C. Eliasson K. Larsson S. Andersson S. T. Hyde R. Nesper H.-G. Von Schnering 《Starch - St?rke》1987,39(5):147-152
The branching geometry of amylopectin according to chemical degradation studies has been combined with the knowledge of packing arrangement of double helices. The structural organization of the polyglucan chains in the crystalline amylopectin units can be described by an infinite periodic minimal surface, and it is closely related to the structure of high-quartz with space group P6422. An important feature of the molecular packing is that the van der Waals distance between double helices is very similar to the length of a linkage formed by the α-1,6-glucoside branching. The physical properties of starch are finally discussed in relation to the proposed structure. 相似文献
986.
The effect of annealing on starch gelatinization behaviour has earlier been described in the literature. The starch: water ratio in these studies have been either very low or very high. In this work the gelatinization behaviour has been studied both with time and temperature at an intermediate starch/water ratio (1:1) by differential scanning calorimetry. Starches from maize, waxy-maize, wheat and potato have been compared. This investigation shows that annealing causes an increase of To and Tm, a narrowing of the gelatinization temperature interval, and a change of the shape of the endotherm can also be observed. The annealing time has to be more than 6 h to induce these changes. 相似文献
987.
Erik Larsson 《Advanced Synthesis \u0026amp; Catalysis》1977,319(6):857-861
The Configurations and Conformations of Some Unsymmetrical S-Substituted 2,3-Dimercapto Succinic Acids Some acids HOOCCH(SR)CH(SR′)COOH (R/R′ = HOOCCH2, C6H5, C6H5CH2 and p-ClC6H4CH2, R ≠ R′) were prepared from HOOCC(SR) CHCOOH and R′SH. Their configurations and conformations were discussed. 相似文献
988.
In this study, base fluid parameters for elastohydrodynamic lubrication (EHL) and friction analyses have been determined experimentally. The viscosity at atmospheric pressure, η0, the pressure‐viscosity index, α, and the EHL friction coefficient, γ, are important parameters in EHL theory and they are crucial in the selection of efficient lubricants for different applications. This investigation focuses on three important lubrication mechanisms: the capability of forming a separating lubricant film, the friction generated in a lubricated contact, and the height of pressure peaks, such as the outlet pressure spike and pressure ripple caused by surface roughness. The influence of different lubricant parameters on these three mechanisms is discussed. The value of α is measured in a Couette high‐pressure viscometer, and the value of γ is obtained from a jumping‐ball device. Other parameters discussed are temperature‐viscosity coefficient, β, bulk modulus, B0, thermal conductivity at atmospheric pressure, λ0, and heat capacity unit volume, ρcp0. A comparison between traditional mineral base oils and environmentally adapted oil based on rapeseed oil and synthetic esters contributes to the further understanding of the performance of these new materials in lubrication applications. It is shown that rapeseed oil and synthetic esters have good lubricating properties and are, in most cases, better than mineral oils. 相似文献
989.
Oil film thickness in hydrodynamic bearings is a fundamental parameter influencing overall hydrodynamic bearing performance. Knowledge of this thickness allows bearing performance to be optimised. For the small hydrodynamic bearings that are usually used in laboratory test facilities, a very small sensor (e.g.,<2 mm) is required because of space limitations. Commercially available eddy‐current and capacitance sensors are too large to be mounted in the pad of such a bearing. An alternative approach is to use sensors based on optical methods, such as the optic lever technique. The main idea in this technique is to detect the intensity of a light beam reflected from a target surface. This intensity is a function of the distance between the sensor and the target. This paper reports the specific features of the optic lever technique as used for measurements of oil film thickness. The design, calibration procedure, and main characteristics of an optical sensor are discussed. A test rig for the calibration of oil film thickness sensors is also presented. The sensor response curve has two parts, linear and non‐linear; using the linear part results in high sensitivity in the micrometre range. The influence of different types of oil on the output signal of the sensor has also been investigated. Experiments with different target velocities have shown that this sensor can be used for accurate and reliable measurement of oil film thickness in hydrodynamic bearings. 相似文献