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Characterisation of gyrase inhibitors using ITC and enzymatic assay = Charakterizace inhibitorů gyrázy s použitím ITC a enzymatického testování : diploma thesis : diplomová práceBarančokova, MichaelaThis paper deals with in vitro evaluation of inhibitors of gyrase and topoisomerase IV - enzymes of type II topoisomerases family. These enzymes are essential for the proper function of bacterial ... cell and their inhibition leads to its destruction. The experimental part of the work had been developed at the Department of Medicinal Chemistry at the University of Ljubljana within Erasmus+ program. Tested novel inhibitors based on substituted pyrroleamide moiety with GyrB (ParE) mechanism of action were developed at the same department. The basic parameters of DNA topology, types and classification of topoisomerases, mechanism of action and structure of gyrase and topoisomerase IV and brief summary of inhibitors used in clinical practice were described. Enzymatic assay was used for evaluation in the experimental part, and half maximal inhibitory concentration IC50 was calculated. The activity against E. coli gyrase, E. coli topoisomerase IV, S. aureus gyrase and S. aureus topoisomerase IV was measured. Results were analyzed and described as structure-activity relationship (SAR) of given compounds. ITC (isothermal titration calorimetry) was carried out for some compounds as complementary analysis and thermodynamic characterization of binding was analyzed. Compounds KMG-15 KMG-17 and NAS-37 were evaluated as the most effective with dual targeting against all tested types of enzymes. Compounds TJL-19, TMK-16, 9-KMG and KMG-11 showed high activity against E. coli gyrase but were not tested against other enzymes. Further experiments will be performed in the future.Vrsta gradiva - magistrsko delo ; neleposlovje za odrasleZaložništvo in izdelava - Ljubljana : [M. Barančoková], 2016Jezik - angleškiCOBISS.SI-ID - 4245617
Avtor
Barančokova, Michaela
Drugi avtorji
Doležal, Martin |
Ilaš, Janez
Teme
topoisomerases |
topoisomerase IV |
inhibitors |
enzymatic assay |
isothermal titration calorimetry
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Barančokova, Michaela | |
Doležal, Martin | |
Ilaš, Janez | 24400 |
Vir: Osebne bibliografije
in: SICRIS
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