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排序方式: 共有210条查询结果,搜索用时 31 毫秒
71.
72.
Luca Laraia Guillaume Garivet Daniel J. Foley Nadine Kaiser Sebastian Müller Sarah Zinken Thomas Pinkert Julian Wilke Dale Corkery Axel Pahl Sonja Sievers Petra Janning Christoph Arenz Yaowen Wu Raphaël Rodriguez Herbert Waldmann 《Angewandte Chemie (International ed. in English)》2020,59(14):5721-5729
Chemical proteomics is widely applied in small‐molecule target identification. However, in general it does not identify non‐protein small‐molecule targets, and thus, alternative methods for target identification are in high demand. We report the discovery of the autophagy inhibitor autoquin and the identification of its molecular mode of action using image‐based morphological profiling in the cell painting assay. A compound‐induced fingerprint representing changes in 579 cellular parameters revealed that autoquin accumulates in lysosomes and inhibits their fusion with autophagosomes. In addition, autoquin sequesters Fe2+ in lysosomes, resulting in an increase of lysosomal reactive oxygen species and ultimately cell death. Such a mechanism of action would have been challenging to unravel by current methods. This work demonstrates the potential of the cell painting assay to deconvolute modes of action of small molecules, warranting wider application in chemical biology. 相似文献
73.
A new amorphous metal-metal alloy Fe90Sc10 has been prepared by single roller melt quenching. Mössbauer spectra above and below the magnetic ordering temperature of 99K have been analysed in terms of distributions of magnetic hyperfine fields and quadrupole splittings. 相似文献
74.
Stephen J. Wagner rey Skripchenko Daniel Robinette James W. Foley Louis Cincotta 《Photochemistry and photobiology》1998,67(3):343-349
A series of four phenothiazine dyes, including methylene blue (MB), were previously tested for their ability to photoinactivate viruses in red cell suspensions. One of the dyes, 1,9-dimethyl-3-dimethylamino-7-dimethylaminophenothiazine (1,9-dimethylmethylene blue), exhibited good intracellular and extracellular virucidal activity for several RNA and DNA viruses under conditions that minimally affected red cell properties. In order to understand why the virucidal specificity of 1, 9-dhnethylmethylene blue was greater than other phenothiazines tested, the physical and chemical properties of the dye were compared to three other closely related analogues (MB, 1,9-dimethyl-3-diethylamino-7-dlbutylaminophenothiazine [compound 4-140], 1,9-dimethyl-3-dimethylamino-7-diethylaminophenothiazine [compound 6-136]). All compounds required light and oxygen for virucidal activity and had relatively high singlet oxygen yields (>0.5), but 1,9-dimethylmethylene blue had a singlet oxygen yield approximately 50% greater than that of MB. In addition, the hydrophobicity/hydophilicity of the compounds varied, with the partition coefficients (2-octanol : water) ranging from 0.11 for MB to 3560 for compound 4-140. The dyes had the following affinities for DNA: 1,9-dimethylmethylene blue > compound 6-136 > MB ~ compound 4-140. This order was similar to the order of activities for photoinactivation of the nonenveloped bacteriophage, R17, by the four compounds. Results with the most hydrophobic compound, 4-140, contrasted with those obtained with 1,9-dimethylmethylene blue. Compound 4-140 had a high affinity for protein and a low affinity for DNA. Although compound 4-140 and light inactivated the nonenveloped bacteriophage R17 poorly, the dye readily photoinactivated enveloped viruses in buffer. However, unlike results with 1,9-dimethylmethylene blue, viral inactivation of enveloped viruses by compound 4-140 was completely inhibited by the presence of red cells and plasma. Thus, the high affinity of 1,9-di-methyymethylene blue for DNA and the dye's efficient singlet oxygen yield suggest viral nucleic acid as a potential target, which could explain the photosensitizer's ability to inactivate viruses without adversely affecting anuclete red cells. 相似文献
75.
The effect of the phase ratio on the electrophoretic and chromatographic properties of unilamellar vesicles comprised of cetyltrimethylammonium bromide (CTAB) and sodium octyl sulfate (SOS) was investigated in EKC. The surfactant concentration of the vesicles was 0.9, 1.2, 1.5, and 1.8% w/v, with a mole ratio of 1:3.66 (CTAB/SOS). Results were compared to those obtained using SDS micelles at concentrations of 1.0% (w/v, 35 mM) and 1.5% (52 mM). The CTAB/SOS vesicles (0.9-1.8% w/v) provided a significantly larger elution range (5.7 < or = t(ves)/t(0) < or = 8.7) and greater hydrophobic (methylene) selectivity (2.8 < or = alpha(CH2) < or = 3.1) than SDS micelles (3.1 < or = t(mc)/t(0) < or = 3.3; alpha(CH2) = 2.2). Whereas the larger elution range can be attributed to the 25% reduction in EOF due to the interaction of unaggregated CTAB cations and the negatively charged capillary wall, the higher methylene selectivity is likely due to the lower concentration of water expected in the CTAB/SOS vesicle bilayer compared to the Palisades layer of SDS micelles. For a given phase ratio, CTAB/SOS vesicles are somewhat less retentive than SDS micelles, although retention factors comparable to those observed in 1.0-1.5% SDS can be obtained with 1.5-1.8% CTAB/SOS. A linear relationship was observed between phase ratio and retention factor, confirming the validity of the phase ratio model for these vesicles. Unique polar group selectivities and positional isomer shape selectivities were obtained with CTAB/SOS vesicles, with both types of selectivities being nearly independent of the phase ratio. For four sets of positional isomers, the elution order was always para < ortho < meta. Finally, the thermodynamics of solute retention was qualitatively similar to that reported for other surfactant aggregates (micelles and microemulsions); the enthalpic contribution to retention was consistently favorable for all compounds, whereas the entropic contribution was favorable only to hydrophobic solutes. 相似文献
76.
(1)H NMR titration experiments have been used to establish that minimal proline-based models show enhanced binding selectivity towards phenol in CDCl(3), relative to other similarly protected amino acid residues. Cooperative binding effects appear to play a role, with sarcosine models affording binding constants to phenol intermediate to those obtained from proline models and other amino acid models. The mechanism for binding, based on DFT calculations and the application of Hunter's molecular recognition toolbox model, cannot be solely attributed to hydrogen bond strength, and appears to be mediated through C-H-pi bonds and the rotational freedom of the amide substrate. 相似文献
77.
A microfluidic device known to mix bulk solutions, the herringbone microchannel, was incorporated into a surface-binding assay to determine if the recirculation of solution altered the binding of a model protein (streptavidin) to the surface. Streptavidin solutions were pumped over surfaces functionalized with its ligand, biotin, and the binding of streptavidin to those surfaces was monitored using surface plasmon resonance imaging. Surface binding was compared between a straight microchannel and herringbone microchannels in which the chevrons were oriented with and against the flow direction. A 3-dimensional finite-element model of the surface binding reaction was developed for each of the geometries and showed strong qualitative agreement with the experimental results. Experimental and model results indicated that the forward and reverse herringbone microchannels substantially altered the distribution of protein binding (2-dimensional binding profile) as a function of time when compared to a straight microchannel. Over short distances (less than 1.5 mm) down the length of the microchannel, the model predicted no additional protein binding in the herringbone microchannel compared to the straight microchannel, consistent with previous findings in the literature. 相似文献
78.
Gonzalez JM Foley MW Bieber NM Bourdelle PA Niedbala RS 《Analytical and bioanalytical chemistry》2011,400(10):3655-3664
Passive exposure to tobacco smoke causes a variety of illnesses ranging from allergic responses to cancer. Assessment of exposure to second-hand tobacco smoke (SHS), particularly among vulnerable populations enables intervention and prevention of future disease. A minimally invasive oral fluids-based onsite test to detect such exposure would create a valuable tool for researchers and clinicians. Here we describe the development of a test that uses an inexpensive reader that utilizes a CMOS image sensor to reliably quantify a reporter signal and determine nicotine exposure. The rapid lateral flow test consists of a nitrocellulose strip with a control line containing goat anti-rabbit IgG, used as an internal standard, and a test line containing BSA-cotinine conjugate. To run the test, diluted sample containing antibodies against cotinine, the major metabolite of nicotine, is mixed with protein A-gold nanoparticles and placed on the sample pad. As the sample runs up to the nitrocellulose pad, antibodies in the running buffer bind to available cotinine. If cotinine is absent, the antibodies will bind to the BSA-cotinine derivative immobilized on the test line, resulting in an intense purple-red band. The concentration of cotinine equivalents in the sample can be estimated from interpretation of the test line. In this article we describe the effect of different cotinine derivatives, oral fluid pretreatment, and application and running buffers on assay sensitivity. The test can reliably detect as little as 2 ng mL(-1) cotinine equivalents. The assay is sensitive, simple, rapid, inexpensive, and easily implementable in point-of-care facilities to detect second-hand smoke exposure. 相似文献
79.
This critical review focuses on the origins and preparation of bio-based surfactants, defined here as non-soap, amphiphilic molecules in which the carbon atoms are derived from annually renewable feedstocks. Environmental concerns and market pressures have led to greater relevance of these chemicals in commercial applications in recent years and extensive research has gone into exploring new classes of surfactants. Highlighted here are examples of bio-based surfactants that are produced on an industrial scale and/or are based on abundant starting materials. The trend of increasing use of renewable resources as starting materials for surfactants is introduced, followed by extensive discussion of the major classes of bio-derived hydrophobes and hydrophiles. Also discussed is the status of research and development with regard to biosynthetically produced surfactants. Finally, concluding remarks address the potential for new surfactant molecular structures as a result of ongoing development in the chemistry of biorefineries, i.e., that the transformation of lignocellulose into fuels is likely to support the manufacturing of new bio-based coproducts (238 references). 相似文献
80.
Denny JA Foley WS Almaraz E Reibenspies JH Bhuvanesh N Darensbourg MY 《Dalton transactions (Cambridge, England : 2003)》2012,41(1):143-148
The synthesis and characterization of bis-mercaptoethanediazaheptane cadmium(II) is reported and compared to the analogous zinc complex. Of significance is the dimeric form of the [Zn(N(2)S(2))](2) complex achieves penta-coordination about zinc through a bridging thiolate whereas cadmium engages two thiolate as S-bridges resulting in hexa-coordination about cadmium within a coordination polymer whose X-ray crystal structure is reported here. In the presence of W(CO)(5), this polymer breaks up, generating dimeric [Cd(N(2)S(2))](2) with two W(CO)(5) units appended to the terminal thiolates, a feat that is not observed for the zinc dimer analogue. The greater thiophilicity of cadmium over zinc is noted in several features of these complexes. 相似文献