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41.
Systematic Comparison of Peptidic Proteasome Inhibitors Highlights the α‐Ketoamide Electrophile as an Auspicious Reversible Lead Motif 下载免费PDF全文
Martin L. Stein Haissi Cui Philipp Beck Christian Dubiella Constantin Voss Prof. Dr. Achim Krüger Prof. Dr. Boris Schmidt Prof. Dr. Michael Groll 《Angewandte Chemie (International ed. in English)》2014,53(6):1679-1683
The ubiquitin–proteasome system (UPS) has been successfully targeted by both academia and the pharmaceutical industry for oncological and immunological applications. Typical proteasome inhibitors are based on a peptidic backbone endowed with an electrophilic C‐terminus by which they react with the active proteolytic sites. Although the peptide moiety has attracted much attention in terms of subunit selectivity, the target specificity and biological stability of the compounds are largely determined by the reactive warheads. In this study, we have carried out a systematic investigation of described electrophiles by a combination of in vitro, in vivo, and structural methods in order to disclose the implications of altered functionality and chemical reactivity. Thereby, we were able to introduce and characterize the class of α‐ketoamides as the most potent reversible inhibitors with possible applications for the therapy of solid tumors as well as autoimmune disorders. 相似文献
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David Rombach Hans‐Achim Wagenknecht 《Angewandte Chemie (International ed. in English)》2020,59(1):300-303
SF6 was applied as pentafluorosulfanylation reagent to prepare ethers with a vicinal SF5 substituent through a one‐step method involving photoredox catalysis. This method shows a broad substrate scope with respect to applicable alcohols for the conversion of α‐methyl and α‐phenyl styrenes. The products bear a new structural motif with two functional groups installed in one step. The alkoxy group allows elimination and azidation as further transformations into valuable pentafluorosulfanylated compounds. These results confirm that non‐toxic SF6 is a useful SF5 transfer reagent if properly activated by photoredox catalysis, and toxic reagents are completely avoided. In combination with light as an energy source, a high level of sustainability is achieved. Through this method, the proposed potential of the SF5 substituent in medicinal chemistry, agrochemistry, and materials chemistry may be exploited in the future. 相似文献
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Johanne Heitmann Solheim Boris Zimmermann Valeria Tafintseva Simona Dzurendov Volha Shapaval Achim Kohler 《Molecules (Basel, Switzerland)》2022,27(6)
Extended multiplicative signal correction (EMSC) is a widely used preprocessing technique in infrared spectroscopy. EMSC is a model-based method favored for its flexibility and versatility. The model can be extended by adding constituent spectra to explicitly model-known analytes or interferents. This paper addresses the use of constituent spectra and demonstrates common pitfalls. It clarifies the difference between analyte and interferent spectra, and the importance of orthogonality between model spectra. Different normalization approaches are discussed, and the importance of weighting in the EMSC is demonstrated. The paper illustrates how constituent analyte spectra can be estimated, and how they can be used to extract additional information from spectral features. It is shown that the EMSC parameters can be used in both regression tasks and segmentation tasks. 相似文献
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Ana Leonor Rivera Miguel Gómez-Lim Francisco Fernández Achim M. Loske 《Physics of life reviews》2012,9(3):308-345
Production of transgenic plants is a routine process for many crop species. Transgenes are introduced into plants to confer novel traits such as improved nutritional qualities, tolerance to pollutants, resistance to pathogens and for studies of plant metabolism. Nowadays, it is possible to insert genes from plants evolutionary distant from the host plant, as well as from fungi, viruses, bacteria and even animals. Genetic transformation requires penetration of the transgene through the plant cell wall, facilitated by biological or physical methods. The objective of this article is to review the state of the art of the physical methods used for genetic plant transformation and to describe the basic physics behind them. 相似文献