| |  Online-Ressource |
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| Verfasst von: | Mühlberg, Eric [VerfasserIn]  |
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| | Umstätter, Florian [VerfasserIn] |
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| | Domhan, Cornelius [VerfasserIn] |
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| | Hertlein, Tobias [VerfasserIn] |
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| | Ohlsen, Knut [VerfasserIn] |
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| | Krause, Andreas [VerfasserIn] |
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| | Kleist, Christian [VerfasserIn] |
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| | Beijer, Barbro [VerfasserIn] |
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| | Zimmermann, Stefan [VerfasserIn] |
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| | Haberkorn, Uwe [VerfasserIn] |
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| | Mier, Walter [VerfasserIn] |
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| | Uhl, Philipp [VerfasserIn] |
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| Titel: | Vancomycin-lipopeptide conjugates with high antimicrobial activity on vancomycin-resistant enterococci |
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| Verf.angabe: | Eric Mühlberg, Florian Umstätter, Cornelius Domhan, Tobias Hertlein, Knut Ohlsen, Andreas Krause, Christian Kleist, Barbro Beijer, Stefan Zimmermann, Uwe Haberkorn, Walter Mier and Philipp Uhl |
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| E-Jahr: | 2020 |
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| Jahr: | 29 May 2020 |
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| Fussnoten: | Gesehen am 01.09.2020 |
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| Titel Quelle: | Enthalten in: Pharmaceuticals |
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| Ort Quelle: | Basel : MDPI, 2004 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 13(2020,6) Artikel-Nummer 110, 14 Seiten |
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| ISSN Quelle: | 1424-8247 |
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| Abstract: | Multidrug-resistant bacteria represent one of the most important health care problems worldwide. While there are numerous drugs available for standard therapy, there are only a few compounds capable of serving as a last resort for severe infections. Therefore, approaches to control multidrug-resistant bacteria must be implemented. Here, a strategy of reactivating the established glycopeptide antibiotic vancomycin by structural modification with polycationic peptides and subsequent fatty acid conjugation to overcome the resistance of multidrug-resistant bacteria was followed. This study especially focuses on the structure–activity relationship, depending on the modification site and fatty acid chain length. The synthesized conjugates showed high antimicrobial potential on vancomycin-resistant enterococci. We were able to demonstrate that the antimicrobial activity of the vancomycin-lipopeptide conjugates depends on the chain length of the attached fatty acid. All conjugates showed good cytocompatibility in vitro and in vivo. Radiolabeling enabled the in vivo determination of pharmacokinetics in Wistar rats by molecular imaging and biodistribution studies. An improved biodistribution profile in comparison to unmodified vancomycin was observed. While vancomycin is rapidly excreted by the kidneys, the most potent conjugate shows a hepatobiliary excretion profile. In conclusion, these results demonstrate the potential of the structural modification of already established antibiotics to provide highly active compounds for tackling multidrug-resistant bacteria. |
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| DOI: | doi:10.3390/ph13060110 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.3390/ph13060110 |
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| | Volltext: https://www.mdpi.com/1424-8247/13/6/110 |
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| | DOI: https://doi.org/10.3390/ph13060110 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | antibiotics |
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| | enterococci |
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| | fatty acids |
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| | multidrug-resistant bacteria |
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| | polycationic peptides |
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| | structural modification |
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| | vancomycin |
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| K10plus-PPN: | 1728566622 |
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| Verknüpfungen: | → Zeitschrift |
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Vancomycin-lipopeptide conjugates with high antimicrobial activity on vancomycin-resistant enterococci / Mühlberg, Eric [VerfasserIn]; 29 May 2020 (Online-Ressource)
