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排序方式: 共有632条查询结果,搜索用时 15 毫秒
1.
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
2.
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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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
5.
Abhendra K. Singh Kaitlyn Kahle Hannah James Allison L. Horner Daniel Villaflor Zach Benedict 《Ceramics International》2021,47(12):17268-17275
In this study the effects of high temperature and moisture on the impact damage resistance and mechanical strength of Nextel 610/alumina silicate ceramic matrix composites were experimentally evaluated. Composite laminates were exposed to either a 1050°C isothermal furnace-based environment for 30 consecutive days at 6 h a day, or 95% relative humidity environment for 13 consecutive days at 67°C. Low velocity impact, tensile and short beam strength tests were performed on both ambient and environmentally conditioned laminates and damage was characterized using a combination of non-destructive and destructive techniques. High temperature and humidity environmental exposure adversely affected the impact resistance of the composite laminates. For all the environments, planar internal damage area was greater than the back side dent area, which in turn was greater than the impactor side dent area. Evidence of environmental embrittlement through a stiffer tensile response was noted for the high temperature exposed laminates while the short beam strength tests showed greater propensity for interlaminar shear failure in the moisture exposed laminates. Destructive evaluations exposed larger, more pronounced delaminations in the environmentally conditioned laminates in comparison to the ambient ones. External damage metrics of the impactor side dent depth and area directly influenced the post-impact tensile strength of the laminates while no such trend between internal damage area and residual strength could be ascertained. 相似文献
6.
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 Baars Julien Engel Lucas Mertens Daniela Meister Carsten Bolm 《Advanced Synthesis \u0026amp; Catalysis》2016,358(14):2293-2299
Carbamoyl fluorides are formed in reactions of hydroxylamines with difluorocarbene generated from sodium bromodifluoroacetate as readily available and non‐toxic carbene precursor. The process shows a high functional group tolerance, and the reaction path has been rationalized by computational calculations.
10.
George M. Burslem Hannah F. Kyle Dr. Alexander L. Breeze Dr. Thomas A. Edwards Prof. Adam Nelson Dr. Stuart L. Warriner Prof. Andrew J. Wilson 《Chembiochem : a European journal of chemical biology》2014,15(8):1083-1087
The therapeutically relevant hypoxia inducible factor HIF‐1α–p300 protein–protein interaction can be orthosterically inhibited with α‐helix mimetics based on an oligoamide scaffold that recapitulates essential features of the C‐terminal helix of the HIF‐1α C‐TAD (C‐terminal transactivation domain). Preliminary SAR studies demonstrated the important role of side‐chain size and hydrophobicity/hydrophilicity in determining potency. These small molecules represent the first biophysically characterised HIF‐1α–p300 PPI inhibitors and the first examples of small‐molecule aromatic oligoamide helix mimetics to be shown to have a selective binding profile. Although the compounds were less potent than HIF‐1α, the result is still remarkable in that the mimetic reproduces only three residues from the 42‐residue HIF‐1α C‐TAD from which it is derived. 相似文献