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Dr. Andreas A. Bastian Dr. Maria Bastian Dr. Manuel Jäger Mark Loznik Dr. Eliza M. Warszawik Xintong Yang Dr. Nabil Tahiri Dr. Peter Fodran Prof. Dr. Martin D. Witte Anne Thoma Dr. Jens Köhler Prof. Dr. Adriaan J. Minnaard Prof. Dr. Andreas Herrmann 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(36):e202200883
The continuous emergence of antimicrobial resistance is causing a threat to patients infected by multidrug-resistant pathogens. In particular, the clinical use of aminoglycoside antibiotics, broad-spectrum antibacterials of last resort, is limited due to rising bacterial resistance. One of the major resistance mechanisms in Gram-positive and Gram-negative bacteria is phosphorylation of these amino sugars at the 3’-position by O-phosphotransferases [APH(3’)s]. Structural alteration of these antibiotics at the 3’-position would be an obvious strategy to tackle this resistance mechanism. However, the access to such derivatives requires cumbersome multi-step synthesis, which is not appealing for pharma industry in this low-return-on-investment market. To overcome this obstacle and combat bacterial resistance mediated by APH(3’)s, we introduce a novel regioselective modification of aminoglycosides in the 3’-position via palladium-catalyzed oxidation. To underline the effectiveness of our method for structural modification of aminoglycosides, we have developed two novel antibiotic candidates overcoming APH(3’)s-mediated resistance employing only four synthetic steps. 相似文献
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The centromere-kinetochore complex is a chromosomal assembly site including repeat motifs and protein binding properties thus mediating chromosome motility and mitotic regulation. Next to the alpha-satellite DNA family as well as human satellite III DNA, contribution of other repetitive sequences has to be strongly considered in centromere function. Here, we report the identification of centromeric 48 bp motifs, isolated from chimpanzee and orang-utan using an orthologous human DNA probe. Applying Southern hybridization we show that these sequences are restricted to hominoid species. Diminishing hybrid formation in gibbons suggested that the 48 bp repeat originated approximately 25-20 million years ago. Consistently, both chimpanzee as well as human repeat probes failed to generate any hybridization signal with the monkey species Cercopithecus aethiops and Aotes trivirgatus. Sequence deviations from the consensus of human repeat monomers of 6% and 10.4% in chimpanzee and orang-utan, respectively, were found within a 16 bp region of the 48 bp repeat units. Gel mobility shift assays using chimpanzee repeat dimers as probes revealed peptide-binding properties with human and chimpanzee nuclear extracts. Species-specific DNA-protein complexes remained unaffected by competition studies and indicated the presence of at least one novel interacting protein consisting of two subunits with 90 and 95 kDa. Our data suggest that the 48 bp repeat, next to alpha-satellite DNA, provides essential sequence information for specific DNA-protein interaction and they imply phylogenetic conservation of these binding properties in primates. The complex is likely involved in the proper formation and/or function of mammalian centromeres. 相似文献
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With 〈·〉 denoting an average with respect to the eigenvalue PDF for the Laguerre unitary ensemble, the object of our study is for I = (0, s) and I = (s, ∞), where χ = 1 for λl ∈ I and χ = 0 otherwise. Using Okamoto's development of the theory of the Painlevé V equation, it is shown that ?N(I; a, μ) is a τ‐function associated with the Hamiltonian therein, and so can be characterized as the solution of a certain second‐order second‐degree differential equation, or in terms of the solution of certain difference equations. The cases μ = 0 and μ = 2 are of particular interest, because they correspond to the cumulative distribution and density function, respectively, for the smallest and largest eigenvalue. In the case I = (s, ∞), ?N(I; a, μ) is simply related to an average in the Jacobi unitary ensemble, and this in turn is simply related to certain averages over the orthogonal group, the unitary symplectic group, and the circular unitary ensemble. The latter integrals are of interest for their combinatorial content. Also considered are the hard‐edge and soft‐edge scaled limits of ?N(I; a, μ). In particular, in the hard‐edge scaled limit it is shown that the limiting quantity ?hard((O, s); a, μ) can be evaluated as a τ‐function associated with the Hamiltonian in Okamoto's theory of the Painlevé III equation. © 2002 Wiley Periodicals, Inc. 相似文献
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A.T. Winzer R. Goldhahn G. Gobsch A. Dadgar H. Witte A. Krtschil A. Krost 《Superlattices and Microstructures》2004,36(4-6):693
Photoreflectance spectroscopy was used to measure the barrier electric field strength F of as-grown AlGaN/GaN heterostructures on Si(111) substrate with two-dimensional electron gases in the temperature range from 80 up to 295 K. The Al-contents were in the range from 12 to 20%. Despite the difference of Al-contents and the large temperature variation we find only minute changes of F. This behaviour is explained by an almost constant strain state and thus a constant piezoelectric polarisation, which was concluded from the analysis of the GaN free excitonic transitions observed by photoluminescence excitation spectroscopy. Self-consistent conduction band calculations point to a pinning of the potential of the bare surface at 0.6 V, attributed to a large density of surface donor states. 相似文献
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Nikolaus Rott Gerassimos Zouzoulas 《Zeitschrift für Angewandte Mathematik und Physik (ZAMP)》1976,48(5):197-224
The problem of thermally driven acoustic oscillations is treated for tubes with variable cross-section, with particular emphasis on the possible reduction of the necessary temperature ratio for excitation. Tubes with optimal conditions in the vicinity of the temperature jump, and with big cross-sections in parts with constant temperature are found to give the best performance in this respect. Included in the family of devices which were treated is the classical Sondhauss-tube. Experiments which give a striking confirmation of the theory are reported. 相似文献