期刊
CHEMBIOCHEM
卷 18, 期 5, 页码 435-440出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201600491
关键词
antibiotics; hydrolysis; ribozymes; RNA
资金
- German Research Council [MA 3442/2-2, BR3783/1-2]
The ever-growing number of pathogenic bacteria resistant to treatment with antibiotics call for the development of novel compounds with as-yet unexplored modes of action. Here, we demonstrate the in vivo antibacterial activity of carba-alpha-D-glucosamine (CGlcN). In this mode of action study, we provide evidence that CGlcN-mediated growth inhibition is due to glmS ribozyme activation, and we demonstrate that CGlcN hijacks an endogenous activation pathway, hence utilizing a prodrug mechanism. This is the first report describing antibacterial activity mediated by activating the self-cleaving properties of a ribozyme. Our results open the path towards a compound class with an entirely novel and distinct molecular mechanism.
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