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排序方式: 共有660条查询结果,搜索用时 31 毫秒
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Dr. Julien J. Freudenreich Dr. Sean Bartlett Dr. Naomi S. Robertson Dr. Sarah L. Kidd Dr. Suzie Forrest Dr. Hannah F. Sore Dr. Warren R. J. D. Galloway Dr. Martin Welch Prof. David R. Spring 《ChemMedChem》2020,15(14):1289-1293
The cylindrocyclophanes are a family of macrocyclic natural products reported to exhibit antibacterial activity. Little is known about the structural basis of this activity due to the challenges associated with their synthesis or isolation. We hypothesised that structural modification of the cylindrocyclophane scaffold could streamline their synthesis without significant loss of activity. Herein, we report a divergent synthesis of the cylindrocyclophane core enabling access to symmetrical macrocycles by means of a catalytic, domino cross-metathesis-ring-closing metathesis cascade, followed by late-stage diversification. Phenotypic screening identified several novel inhibitors of methicillin-resistant Staphylococcus aureus. The most potent inhibitor has a unique tetrabrominated [7,7]paracyclophane core with no known counterpart in nature. Together these illustrate the potential of divergent synthesis using catalysis and unbiased screening methods in modern antibacterial discovery. 相似文献
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Anh K. Lam Hannah Panlilio Jennifer Pusavat Cassandra L. Wouters Erika L. Moen Prof. Robert E. Brennan Prof. Charles V. Rice 《ChemMedChem》2020,15(15):1421-1428
Infections from antibiotic-resistant Staphylococcus aureus and Pseudomonas aeruginosa are a serious threat because reduced antibiotic efficacy complicates treatment decisions and prolongs the disease state in many patients. To expand the arsenal of treatments against antimicrobial-resistant (AMR) pathogens, 600-Da branched polyethylenimine (BPEI) can overcome antibiotic resistance mechanisms and potentiate β-lactam antibiotics against Gram-positive bacteria. BPEI binds cell-wall teichoic acids and disables resistance factors from penicillin binding proteins PBP2a and PBP4. This study describes a new mechanism of action for BPEI potentiation of antibiotics generally regarded as agents effective against Gram-positive pathogens but not Gram-negative bacteria. 600-Da BPEI is able to reduce the barriers to drug influx and facilitate the uptake of a non-β-lactam co-drug, erythromycin, which targets the intracellular machinery. Also, BPEI can suppress production of the cytokine interleukin IL-8 by human epithelial keratinocytes. This enables BPEI to function as a broad-spectrum antibiotic potentiator, and expands the opportunities to improve drug design, antibiotic development, and therapeutic approaches against pathogenic bacteria, especially for wound care. 相似文献
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Maxwell A. Astle Graham A. Rance Hannah J. Loughlin Thomas D. Peters Andrei N. Khlobystov 《Advanced functional materials》2019,29(17)
The principle of a “catalytic nanosponge” that combines the catalysis of organosulfur oxidation and sequestration of the products from reaction mixtures is demonstrated. Group VI metal oxide nanoparticles (CrOx, MoOx, WOx) are embedded within hollow graphitized carbon nanofibers (GNFs), which act as nanoscale reaction vessels for oxidation reactions used in the decontamination of fuel. When immersed in a model liquid alkane fuel contaminated with organosulfur compounds (benzothiophene, dibenzothiophene, dimethyldibenzothiophene), it is found that MoO2@GNF nanoreactors, comprising 30 nm molybdenum dioxide nanoparticles grown within the channel of GNFs, show superior abilities toward oxidative desulfurization (ODS), affording over 98% sulfur removal at only 5.9 mol% catalyst loading. The role of the carbon nanoreactor in MoO2@GNF is to enhance the activity and stability of catalytic centers over at least 5 cycles. Surprisingly, the nanotube cavity can selectively absorb and remove the ODS products (sulfoxides and sulfones) from several model fuel systems. This effect is related to an adsorptive desulfurization (ADS) mechanism, which in combination with ODS within the same material, yields a “catalytic nanosponge” MoO2@GNF. This innovative ODS and ADS synergistic functionality negates the need for a solvent extraction step in fuel desulfurization and produces ultralow sulfur fuel. 相似文献
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Hannah Welte Prof. Dr. Michael Kovermann 《Chembiochem : a European journal of chemical biology》2020,21(24):3575-3579
In living organisms, protein folding and function take place in an inhomogeneous, highly crowded environment possessing a concentration of diverse macromolecules of up to 400 g/L. It has been shown that the intracellular environment has a pronounced effect on the stability, dynamics and function of the protein under study, and has for this reason to be considered. However, most protein studies neglect the presence of these macromolecules. Consequently, we probe here the overall thermodynamic stability of cold shock protein B from Bacillus subtilis (BsCspB) in cell lysate. We found that an increase in cell lysate concentration causes a monotonic increase in the thermodynamic stability of BsCspB. This result strongly underlines the importance of considering the biological environment when inherent protein parameters are quantitatively determined. Moreover, we demonstrate that targeted application of 19F NMR spectroscopy operates as an ideal tool for protein studies performed in complex cellular surroundings. 相似文献
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Hannah C. Nerl Anuj Pokle Lewys Jones Knut Müller‐Caspary Karel H. W. van den Bos Clive Downing Eoin K. McCarthy Nicolas Gauquelin Quentin M. Ramasse Ivan Lobato Dermot Daly Juan Carlos Idrobo Sandra Van Aert Gustaaf Van Tendeloo Stefano Sanvito Jonathan N. Coleman Clotilde S. Cucinotta Valeria Nicolosi 《Advanced functional materials》2019,29(37)
The fabrication of 2D systems for electronic devices is not straightforward, with top‐down low‐yield methods often employed leading to irregular nanostructures and lower quality devices. Here, a simple and reproducible method to trigger self‐assembly of arrays of high aspect‐ratio chiral copper heterostructures templated by the structural anisotropy in black phosphorus (BP) nanosheets is presented. Using quantitative atomic resolution aberration‐corrected scanning transmission electron microscopy imaging, in situ heating transmission electron microscopy and electron energy‐loss spectroscopy arrays of heterostructures forming at speeds exceeding 100 nm s?1 and displaying long‐range order over micrometers are observed. The controlled instigation of the self‐assembly of the Cu heterostructures embedded in BP is achieved using conventional electron beam lithography combined with site specific placement of Cu nanoparticles. Density functional theory calculations are used to investigate the atomic structure and suggest a metallic nature of the Cu heterostructures grown in BP. The findings of this new hybrid material with unique dimensionality, chirality, and metallic nature and its triggered self‐assembly open new and exciting opportunities for next generation, self‐assembling devices. 相似文献