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dc.contributor.authorMeiers, Joscha
dc.contributor.authorZahorska, Eva
dc.contributor.authorRöhrig, Teresa
dc.contributor.authorHauck, Dirk
dc.contributor.authorWagner, Stefanie
dc.contributor.authorTitz, Alexander
dc.date.accessioned2020-11-27T15:02:09Z
dc.date.available2020-11-27T15:02:09Z
dc.date.issued2020-10-02
dc.identifier.citationJ Med Chem. 2020 Oct 22;63(20):11707-11724. doi: 10.1021/acs.jmedchem.0c00856. Epub 2020 Oct 2.en_US
dc.identifier.pmid32924479
dc.identifier.doi10.1021/acs.jmedchem.0c00856
dc.identifier.urihttp://hdl.handle.net/10033/622620
dc.description.abstractChronic infections by Pseudomonas aeruginosa are characterized by biofilm formation, which effectively enhances resistance toward antibiotics. Biofilm-specific antibiotic delivery could locally increase drug concentration to break antimicrobial resistance and reduce the drug's peripheral side effects. Two extracellular P. aeruginosa lectins, LecA and LecB, are essential structural components for biofilm formation and thus render a possible anchor for biofilm-targeted drug delivery. The standard-of-care drug ciprofloxacin suffers from severe systemic side effects and was therefore chosen for this approach. We synthesized several ciprofloxacin-carbohydrate conjugates and established a structure-activity relationship. Conjugation of ciprofloxacin to lectin probes enabled biofilm accumulation in vitro, reduced the antibiotic's cytotoxicity, but also reduced its antibiotic activity against planktonic cells due to a reduced cell permeability and on target activity. This work defines the starting point for new biofilm/lectin-targeted drugs to modulate antibiotic properties and ultimately break antimicrobial resistance.en_US
dc.language.isoenen_US
dc.publisherACSen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleDirecting Drugs to Bugs: Antibiotic-Carbohydrate Conjugates Targeting Biofilm-Associated Lectins of Pseudomonas aeruginosa .en_US
dc.typeArticleen_US
dc.identifier.eissn1520-4804
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalJournal of medicinal chemistryen_US
dc.source.volume63
dc.source.issue20
dc.source.beginpage11707
dc.source.endpage11724
refterms.dateFOA2020-11-27T15:02:10Z
dc.source.journaltitleJournal of medicinal chemistry
dc.source.countryUnited States


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International