Pang, Lijuan. Antagonizing the adhesion of type 1 fimbriae - mediated Escherichia coli - a novel therapy for urinary tract infections. 2015, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_11266
To achieve oral bioavailability, to improve binding affinity, and to explore the binding mode, we chemically modified the biphenyl FimH antagonists with diverse strategies. To establish the designed compound libraries, traditional synthesis and dynamic combinatorial techniques were applied. The binding affinity and the thermodynamic profile of the antagonists were evaluated by a cell-free competitive binding assay, a competitive fluorescence polarization assay, a cell-based flow cytometry assay, and isothermal titration calorimetry (ITC). Furthermore, the PK properties were determined by in vitro and in vivo assays. As results, structure-activity and structure-property relationships were established for structurally diversified FimH antagonists. The reported strategies led to FimH antagonists with significantly improved PD/PK profile regarding effectiveness of the anti-adhesive treatment.
|Committee Members:||Buschauer, Armin|
|Faculties and Departments:||05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molekulare Pharmazie (Ernst)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||434 S.|
|Last Modified:||30 Jun 2016 10:58|
|Deposited On:||06 Aug 2015 08:18|
Repository Staff Only: item control page