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51.
Nicki Frederiksen Assoc. Prof. Paul R. Hansen Dr. Dorota Zabicka Magdalena Tomczak Malgorzata Urbas Dr. Ilona Domraceva Prof. Fredrik Björkling Assoc. Prof. Henrik Franzyk 《ChemMedChem》2020,15(24):2544-2561
The influence of hydrophobicity on antibacterial activity versus the effect on the viability of mammalian cells for peptide/peptoid hybrids was examined for oligomers based on the cationic Lys-like peptoid residue combined with each of 28 hydrophobic amino acids in an alternating sequence. Their relative hydrophobicity was correlated to activity against both Gram-negative and Gram-positive species, human red blood cells, and HepG2 cells. This identified hydrophobic side chains that confer potent antibacterial activity (e. g., MICs of 2–8 μg/mL against E. coli) and low toxicity toward mammalian cells (<10 % hemolysis at 400 μg/mL and IC50>800 μg/mL for HepG2 viability). Most peptidomimetics retained activity against drug-resistant strains. These findings corroborate the hypothesis that for related peptidomimetics two hydrophobicity thresholds may be identified: i) it should exceed a certain level in order to confer antibacterial activity, and ii) there is an upper limit, beyond which cell selectivity is lost. It is envisioned that once identified for a given subclass of peptide-like antibacterials such thresholds can guide further optimisation. 相似文献
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Maria Luisa Introvigne Magdalena A. Taracila Prof. Fabio Prati Prof. Emilia Caselli Prof. Robert A. Bonomo 《ChemMedChem》2020,15(14):1283-1288
Boronic acids are known reversible covalent inhibitors of serine β-lactamases. The selectivity and high potency of specific boronates bearing an amide side chain that mimics the β-lactam's amide side chain have been advanced in several studies. Herein, we describe a new class of boronic acids in which the amide group is replaced by a bioisostere triazole. The boronic acids were obtained in a two-step synthesis that relies on the solid and versatile copper-catalyzed azide–alkyne cycloaddition (CuAAC) followed by boronate deprotection. All of the compounds show very good inhibition of the Klebsiella pneumoniae carbapenemase KPC-2, with Ki values ranging from 1 nM to 1 μM, and most of them are able to restore cefepime activity against K. pneumoniae harboring blaKPC-2. In particular, compound 1 e , bearing a sulfonamide substituted by a thiophene ring, proved to be an excellent KPC-2 inhibitor (Ki=30 nM); it restored cefepime susceptibility in KPC-Kpn cells (MIC=0.5 μg/mL) with values similar to that of vaborbactam (Ki=20 nM, MIC in KPC-Kpn 0.5 μg/mL). Our findings suggest that α-triazolylboronates might represent an effective scaffold for the treatment of KPC-mediated infections. 相似文献
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Joanna Jaskowiak Jolanta Kwasniewska Miriam Szurman-Zubrzycka Magdalena Rojek-Jelonek Paul B. Larsen Iwona Szarejko 《International journal of molecular sciences》2020,21(22)
ATR, a DNA damage signaling kinase, is required for cell cycle checkpoint regulation and detecting DNA damage caused by genotoxic factors including Al3+ ions. We analyzed the function of the HvATR gene in response to chemical clastogen-maleic acid hydrazide (MH). For this purpose, the Al-tolerant barley TILLING mutant hvatr.g was used. We described the effects of MH on the nuclear genome of hvatr.g mutant and its WT parent cv. “Sebastian”, showing that the genotoxic effect measured by TUNEL test and frequency of cells with micronuclei was much stronger in hvatr.g than in WT. MH caused a significant decrease in the mitotic activity of root cells in both genotypes, however this effect was significantly stronger in “Sebastian”. The impact of MH on the roots cell cycle, analyzed using flow cytometry, showed no differences between the mutant and WT. 相似文献
54.
Witold Brostow Ligia Gargallo Andrea Hormazabal Magdalena Jaklewicz Kevin P Menard Alejandra Opazo Deodato Radic 《Polymer International》2004,53(4):460-464
We have studied blends of a polymer liquid crystal (PLC) with poly(cyclohexylethyl methacrylate) (PCHEMA) or poly(cyclohexylpropyl methacrylate) (PCHPMA). The PLC is PET/0.6PHB where PET = poly(ethylene terephthalate), PHB = p-hydroxybenzoic acid and 0.6 is the mole fraction of the latter in the copolymer. The microstructure was studied by scanning electron microscopy (SEM). PCHEMA + PLC (20 wt% of the latter, blend E) has a fine texture with LC islands evenly distributed in the matrix and good adhesion between the phases resulting from their partial miscibility. The PCHPMA + PLC (20 wt% of the latter, blend P) shows only limited compatibility. The SEM results are confirmed by values of the glass transition temperatures Tg determined via thermal mechanical analysis. The Tg value of the blend E is shifted towards the Tg of PLC; Tg of blend P is practically equal to that of PCHPMA. The linear isobaric expansivity αL values for both blends are lower than the respective values for pure PCHPMA and PCHEMA. Thermal stabilities of the blends determined by thermogravimetry are also better than those of pure polymethacrylates. The temperature of 50% weight degradation for blend E is higher than that for pure PCHEMA by more than 60 K Copyright © 2004 Society of Chemical Industry 相似文献
55.
Multiscale approach to the morphology,structure, and segmental dynamics of complex degradable aliphatic polyurethanes 下载免费PDF全文
Milena Špírková Luďka Machová Libor Kobera Jiří Brus Rafał Poręba Magdalena Serkis Alexander Zhigunov 《应用聚合物科学杂志》2015,132(10)
A multiscale approach spanning from the segmental (subnanometer) up to micrometer level was applied for detailed study of the self‐assembly of aliphatic block polyurethane (PU) elastomers. To understand the principles of the self‐organization of hard and soft segments in the complex multi‐component systems, several two‐component model PU samples, that is, the products of 1,6‐diisocyanatohexane (HDI) with three diols differing in the length and constitution were also prepared, characterized, and investigated: (i) polycarbonate‐based macrodiol (MD), (ii) biodegradable oligomeric diol (DL‐L; product of butane‐1,4‐diol and D,L‐lactide), and (iii) butane‐1,4‐diol (BD). The study (particularly 13C‐1H PILGRIM NMR spectra) reveals complex internal organization and interesting (application appealing) behavior of multi‐component PUs. Hard segments (HDI+BD products) feature self‐assembled and significantly folded chain conformations with interdomain spacing 15–22 nm (small‐angle X‐ray scattering analysis). The small domains are hierarchically assembled in various structural formations of µm size (spherulites) depending on PU composition, as detected by transmission electron microscopy and atomic force microscopy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41590. 相似文献
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Andreas Winkel Wibke Dempwolf Eva Gellermann Magdalena Sluszniak Sebastian Grade Wieland Heuer Michael Eisenburger Henning Menzel Meike Stiesch 《International journal of molecular sciences》2015,16(2):4327-4342
Peri-implant infections from bacterial biofilms on artificial surfaces are a common threat to all medical implants. They are a handicap for the patient and can lead to implant failure or even life-threatening complications. New implant surfaces have to be developed to reduce biofilm formation and to improve the long-term prognosis of medical implants. The aim of this study was (1) to develop a new method to test the antibacterial efficacy of implant surfaces by direct surface contact and (2) to elucidate whether an innovative antimicrobial copolymer coating of 4-vinyl-N-hexylpyridinium bromide and dimethyl(2-methacryloyloxyethyl) phosphonate (VP:DMMEP 30:70) on titanium is able to reduce the attachment of bacteria prevalent in peri-implant infections. With a new in vitro model with semi-coated titanium discs, we were able to show a dramatic reduction in the adhesion of various pathogenic bacteria (Streptococcus sanguinis, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis), completely independently of effects caused by soluble materials. In contrast, soft tissue cells (human gingival or dermis fibroblasts) were less affected by the same coating, despite a moderate reduction in initial adhesion of gingival fibroblasts. These data confirm the hypothesis that VP:DMMEP 30:70 is a promising antibacterial copolymer that may be of use in several clinical applications. 相似文献
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59.
Gheorghe Virgil Aldica Magdalena Lidia Ciurea Dorina Magdalena Chipara Ana Maria Lepadatu Karen Lozano Ionel Stavarache Stelian Popa Mircea Chipara 《应用聚合物科学杂志》2017,134(38)
Nanocomposites have been obtained by dispersing various amounts of vapor grown carbon nanofibers within isotactic polypropylene. Thermal investigations done by differential scanning calorimetry and dynamic mechanical analysis revealed the effect of the vapor grown carbon nanofibers on the melting, crystallization, α, and β relaxations. Direct current electrical features of these nanocomposites have been investigated and related to the thermal features of these nanocomposites. The effect of the loading with carbon nanofibers on the electrical properties of these nanocomposites is discussed within the percolation theory. The percolation threshold was estimated at about 5.5% wt carbon nanofibers. The temperature dependence of the direct current conductivity is analyzed in detail and it is concluded that the electronic hopping is the dominant transport mechanism. A transition from one‐dimensional hopping towards a three‐dimensional hopping was noticed as the concentration of carbon nanofibers was increased from 10% wt to 20% wt carbon nanofiber. The possibility of a differential negative resistivity is suggested. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45297. 相似文献
60.
AbstractThe aim of this study was to evaluate the effect of convective and cryogenic freezing, hot air convective drying (HACD) at 60, 70, 80, and 90?°C and microwave vacuum drying (MWVD) at 100, 150, 200, 300, 450, and 500?W on the drying kinetics and texture of whole cranberries. Effective moisture diffusivities and drying rates were higher, whereas drying times were shorter for the samples dried by MWVD compared with the samples processed by HACD. The drying kinetics of cranberries during MWVD was discussed based on the hypothesis postulating that changes in the drying rate of cranberries during MWVD can be explained by and correlated with changes in the pressure gradient on material surface. Cranberries processed by MWVD were characterized by significantly greater hardness, gumminess, and chewiness in comparison with HACD samples. MWVD was found to be an effective method for producing dried snacks characterized by hard and crispy texture and considerable resistance to stress associated with manufacturing, packaging, storage, and delivery. HACD produced brittle fruit that were difficult to store and transport and were not fully suitable for direct consumption. Convective freezing before MWVD improved the overall appearance of cranberries, whereas cryogenic freezing combined with high temperature HACD adversely influenced the drying rate and produced dried cranberries with suboptimal overall appearance. 相似文献