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排序方式: 共有289条查询结果,搜索用时 125 毫秒
191.
Adibekian A Martin BR Chang JW Hsu KL Tsuboi K Bachovchin DA Speers AE Brown SJ Spicer T Fernandez-Vega V Ferguson J Hodder PS Rosen H Cravatt BF 《Journal of the American Chemical Society》2012,134(25):10345-10348
The development of small-molecule inhibitors for perturbing enzyme function requires assays to confirm that the inhibitors interact with their enzymatic targets in vivo. Determining target engagement in vivo can be particularly challenging for poorly characterized enzymes that lack known biomarkers (e.g., endogenous substrates and products) to report on their inhibition. Here, we describe a competitive activity-based protein profiling (ABPP) method for measuring the binding of reversible inhibitors to enzymes in animal models. Key to the success of this approach is the use of activity-based probes that show tempered rates of reactivity with enzymes, such that competition for target engagement with reversible inhibitors can be measured in vivo. We apply the competitive ABPP strategy to evaluate a newly described class of piperazine amide reversible inhibitors for the serine hydrolases LYPLA1 and LYPLA2, two enzymes for which selective, in vivo active inhibitors are lacking. Competitive ABPP identified individual piperazine amides that selectively inhibit LYPLA1 or LYPLA2 in mice. In summary, competitive ABPP adapted to operate with moderately reactive probes can assess the target engagement of reversible inhibitors in animal models to facilitate the discovery of small-molecule probes for characterizing enzyme function in vivo. 相似文献
192.
Tomlinson-Phillips J Davis J Ben-Amotz D Spångberg D Pejov L Hermansson K 《The journal of physical chemistry. A》2011,115(23):6177-6183
Molecular dynamics and electric field strength simulations are performed in order to quantify the structural, dynamic, and vibrational properties of non-H-bonded (dangling) OH groups in the hydration shell of neopentane, as well as in bulk water. The results are found to be in good agreement with the experimentally observed high-frequency (~3660 cm(-1)) OH band arising from the hydration shell of neopentanol dissolved in HOD/D(2)O, obtained by analyzing variable concentration Raman spectra using multivariate curve resolution (Raman-MCR). The simulation results further indicate that hydration shell dangling OH groups preferentially point toward the central carbon atom of neopentane to a degree that increases with the lifetime of the dangling OH. 相似文献
193.
Generalizing the work of Farahat-Higman on symmetric groups, we describe the structures of the even centers
of integral spin symmetric group superalgebras, which lead to universal algebras termed as the spin FH-algebras. A connection
between the odd Jucys-Murphy elements and the Catalan numbers is developed and then used to determine the algebra generators
of the spin FH-algebras and of the even centers
. 相似文献
194.
Darren Greetham Jill Vickerstaff Daniel Shenton Gabriel G Perrone Ian W Dawes Chris M Grant 《BMC biochemistry》2010,11(1):3
Background
Protein-SH groups are amongst the most easily oxidized residues in proteins, but irreversible oxidation can be prevented by protein glutathionylation, in which protein-SH groups form mixed disulphides with glutathione. Glutaredoxins and thioredoxins are key oxidoreductases which have been implicated in regulating glutathionylation/deglutathionylation in diverse organisms. Glutaredoxins have been proposed to be the predominant deglutathionylase enzymes in many plant and mammalian species, whereas, thioredoxins have generally been thought to be relatively inefficient in deglutathionylation. 相似文献195.
Mitchell P. Sternlieb Jill D. Pasteris Benjamin R. Williams Katherine A. Krol Claude H. Yoder 《Polyhedron》2010
The properties of carbonated hydroxyl and chloro lead apatites, Pb10(PO4)6(OH)2 and Pb10(PO4)6Cl2, serve as models for the incorporation of carbonate into their medically important calcium analogs, and there is likely incorporation of carbonate in an insoluble lead phosphate phase during lead remediation. We have synthesized a series of carbonated lead hydroxyl- and lead chloro-apatites at 60–80 °C. The incorporation of carbonate into the apatite structure was documented by X-ray powder diffraction, IR and Raman spectroscopy, 207Pb solid state NMR spectroscopy, and elemental analysis. The carbonate content was determined by combustion analysis and confirmed by Raman spectroscopic analysis. As carbonate content increases in hydroxyl lead apatite, Raman spectra show changes in the phosphate stretching modes at 925 and 950 cm−1, an increase in intensity and downshift of a new peak at 1050 cm−1, and changes in the spectral features of the O–H stretch at about 3560 cm−1. The variation in unit cell parameters for the chloro lead apatite as a function of carbonate content is similar to that documented for B-type substitution in calcium apatites. The 207Pb NMR spectra corroborate B-type substitution. For the hydroxyl lead apatite, the changes in cell parameters suggest a combination of A- and B-type substitution. Solubilities of the carbonated lead apatites, determined by ICP-MS, increase slightly at low to moderate carbonate content, but more strongly at ca. 5.0 wt.% carbonate content. Ksp values extrapolated to zero carbonate content reveal that the chloro lead apatite is indeed less soluble than the hydroxyl analog. 相似文献
196.
Cameron Scott Sarah Cameron Jill Cundell Ashish Mathur James Davis 《Current Opinion in Electrochemistry》2020
Moisture plays a critical role in the wound healing process and, given the multitude of electrochemical sensors aimed at measuring humidity, it is somewhat surprising that there are few systems dedicated to this particular application. The issues relating to wound moisture and the practical challenges facing the adaptation of generic resistive moisture sensors to this area are considered along with the potential impact such systems could have on nursing practice. 相似文献
197.
198.
Progress in developing a new measurement method for ultrasound output power is described. It is a thermal-based technique with the acoustic power generated by a transducer being absorbed within a specially developed polyurethane rubber material, whose high absorption coefficient ensures energy deposition within a few mm of the ultrasonic wave entering the material. The rate of change of temperature at the absorber surface is monitored using the pyroelectric voltage generated from electrodes disposed either side of a 60 mm diameter, 0.061 mm thick membrane of the piezoelectric polymer polyvinylidene fluoride (pvdf) bonded to the absorber. The change in the pyroelectric output voltage generated by the sensor when the transducer is switched ON and OFF is proportional to the delivered ultrasound power. The sensitivity of the device is defined as the magnitude of these switch voltages to a unit input stimulus of power (watt). Three important aspects of the performance of the pyroelectric sensor have been studied. Firstly, measurements have revealed that the temperature dependent sensitivity increases over the range from approximately 20 °C to 30 °C at a rate of +1.6% °C−1. Studies point to the key role that the properties of both the absorbing backing layer and pvdf membrane play in controlling the sensor response. Secondly, the high sensitivity of the technique has been demonstrated using an NPL Pulsed Checksource, a 3.5 MHz focused transducer delivering a nominal acoustic power level of 4 mW. Finally, proof-of-concept of a new type of acoustic sensor responding to time-averaged intensity has been demonstrated, through fabrication of an absorber-backed hydrophone of nominal active element diameter 0.4 mm. A preliminary study using such a device to resolve the spatial distribution of acoustic intensity within plane-piston and focused 3.5 MHz acoustic fields has been completed. Derived beam profiles are compared to conventional techniques that depend on deriving intensity from acoustic pressure measurements made using the sensor as a calibrated hydrophone. 相似文献
199.
Grob JE Nunez J Dechantsreiter MA Hamann LG 《The Journal of organic chemistry》2011,76(24):10241-10248
The efficient preparation of heterocycles with a range of substitutions ortho to heteroatoms remains as a challenge in organic synthesis, particularly relevant to the construction of druglike molecules due to the ubiquitous presence of such moieties in that chemical space. Modular installation of heterocyclic building blocks using Suzuki-Miyaura cross-coupling is a conceptually useful strategy to address this challenge, though this has historically been met with technical difficulty due to issues of inaccessibility and instability of the requisite heterocyclic boronates. Herein we report a mild and highly regioselective cycloaddition approach which affords convenient access to stable MIDA boronate-functionalized isoxazoles and triazoles and their subsequent efficient Suzuki-Miyaura cross-coupling. This methodology is then further applied to a set of druglike compounds in an efficient one-pot telescoped sequence in line with green chemistry principles. 相似文献
200.
Hoerner R Feldpausch J Gray RL Curry S Islam Z Goldy T Klein F Tadese T Rice J Mozola M 《Journal of AOAC International》2011,94(5):1467-1480
Reveal Salmonella 2.0 is an improved version of the original Reveal Salmonella lateral flow immunoassay and is applicable to the detection of Salmonella enterica serogroups A-E in a variety of food and environmental samples. A Performance Tested Method validation study was conducted to compare performance of the Reveal 2.0 method with that of the U.S. Department of Agriculture-Food Safety and Inspection Service or U.S. Food and Drug Administration/Bacteriological Analytical Manual reference culture methods for detection of Salmonella spp. in chicken carcass rinse, raw ground turkey, raw ground beef, hot dogs, raw shrimp, a ready-to-eat meal product, dry pet food, ice cream, spinach, cantaloupe, peanut butter, stainless steel surface, and sprout irrigation water. In a total of 17 trials performed internally and four trials performed in an independent laboratory, there were no statistically significant differences in performance of the Reveal 2.0 and reference culture procedures as determined by Chi-square analysis, with the exception of one trial with stainless steel surface and one trial with sprout irrigation water where there were significantly more positive results by the Reveal 2.0 method. Considering all data generated in testing food samples using enrichment procedures specifically designed for the Reveal method, overall sensitivity of the Reveal method relative to the reference culture methods was 99%. In testing environmental samples, sensitivity of the Reveal method relative to the reference culture method was 164%. For select foods, use of the Reveal test in conjunction with reference method enrichment resulted in overall sensitivity of 92%. There were no unconfirmed positive results on uninoculated control samples in any trials for specificity of 100%. In inclusivity testing, 102 different Salmonella serovars belonging to serogroups A-E were tested and 99 were consistently positive in the Reveal test. In exclusivity testing of 33 strains of non-salmonellae representing 14 genera, 32 were negative when tested with Reveal following nonselective enrichment, and the remaining strain was found to be substantially inhibited by the enrichment media used with the Reveal method. Results of ruggedness testing showed that the Reveal test produces accurate results even with substantial deviation in sample volume or device development time. 相似文献