Design and Synthesis of the Substrate and Inhibitors for Study of Bacterial Transglycosylation
Date Issued
2008
Date
2008
Author(s)
Hsu, Yu-Fang
Abstract
The use of antibiotics has dominated therapies for bacterial infections over the past decades. Nevertheless, the emergence of antimicrobial resistance has become a serious problem and has created a major threat to public health. It is obvious that development of new antibiotics is in an urgent need. The cell wall is essential for bacterial life because of its tolerance towards the high internal osmotic pressures. An essential constituent of bacterial cell wall is the peptidoglycan. Our approach to develop new antibiotics is to inhibit transglycosylase (TG), a specific enzyme, in peptidoglycan biosynthesis pathway. n the first place, we demonstrated the synthesis of Lipid II, the natural substrate of transglycosylase, and applied to establish transglycosylase activity assay. n the second place, we chose a specific saccharide as the core structure to mimic the transition-state of the polymerization of Lipid II during transglycosylation. everal compounds were developed as possible transglycosylase inhibitors on the basis of the molecular docking model and screened for the transglycosylase activity assay and MIC assay. Through these compounds did not show the desired TG inhibition of antibacterial activity, discovery of an efficient inhibitor of transglycosylase may promise the development of potent antibiotics in the future.
Subjects
transglycosylase
peptidoglycan
Lipid II
SDGs
Type
thesis
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