Total Synthesis of Lipid II and Analogs for the Study of Transglycosylation in Cell Wall Formation
| Autor: | Chen-Yu Liu, 劉朕與 |
|---|---|
| Rok vydání: | 2008 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 96 Since the discovery of penicillin by Fleming more than 80 years ago, antibiotics have been needed to treat infections caused by bacteria. However, even vancomycin, a potent antibiotic as the final weapon against bacterial infections, has encountered the problem of drug resistance. The development of new antibiotic to treat resistant bacterial infections is an important issue for public health. Transglycosylase (TG) is a potential target for development of new antibiotics. It is located on the extracellular surface of the bacterial cell membrane, where it catalyzes the polymerization of lipid II to establish the bacterial cell wall. One of the difficulties in studying TG is the lack of lipid II, though it can be isolated from bacterial membrane in little amount by tedious procedure. In this thesis, I report a chemical synthesis that provides an alternative method to obtain substantial amounts of lipid II and its analogues containing four cis-isoprene units. Furthermore, the natural lipid II and its analogues were elaborated with fluorescence probes, for example, dansyl, fluorescein, and naphthyl via chemical methods. These fluorescent substrates were used to study the transglycosylation in cell wall formation. The reactivity between lipid II analogs and PBP1b were moitored by HPLC using fluorescence detector. Based on the analysis, fluorescein conjugated with Fluorescein-LII is too bulky to be recognized by TG, but Dansyl-LII, D-C20-LII, and FRET-LII are still the substrates of TG. By normalization with internal standard, we may screen the inhibitors based on the decrease of D-C20-LII monitored by HPLC. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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