Fluoro-Carba-Sugars are Glycomimetic Activators of the glmS Ribozyme

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2017
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Matzner, Daniel
Schüller, Anna
Mayer, Günter
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The glmS ribozyme is a bacterial gene-regulating riboswitch that controls cell wall synthesis, depending on glucosamine-6-phosphate as a cofactor. Due to the presence of this ribozyme in several human pathogen bacteria (e.g., MRSA, VRSA), the glmS ribozyme represents an attractive target for the development of artificial cofactors. The substitution of the ring oxygen in carbohydrates by functionalized methylene groups leads to a new generation of glycomimetics that exploits distinct interaction possibilities with their target structure in biological systems. Herein, we describe the synthesis of mono-fluoro-modified carba variants of α-d-glucosamine and β-l-idosamine. (5aR)-Fluoro-carba-α-d-glucosamine-6-phosphate is a synthetic mimic of the natural ligand of the glmS ribozyme and is capable of effectively addressing its unique self-cleavage mechanism. However, in contrast to what was expected, the activity is significantly decreased compared to its non-fluorinated analog. By combining self-cleavage assays with the Bacillus subtilis and Staphylococcus aureus glmS ribozyme and molecular docking studies, we provide a structure-activity relationship for fluorinated carba-sugars.

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ISO 690MATZNER, Daniel, Anna SCHÜLLER, Torben SEITZ, Valentin WITTMANN, Günter MAYER, 2017. Fluoro-Carba-Sugars are Glycomimetic Activators of the glmS Ribozyme. In: Chemistry - A European Journal. 2017, 23(51), pp. 12604-12612. ISSN 0947-6539. eISSN 1521-3765. Available under: doi: 10.1002/chem.201702371
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@article{Matzner2017-09-12Fluor-40546,
  year={2017},
  doi={10.1002/chem.201702371},
  title={Fluoro-Carba-Sugars are Glycomimetic Activators of the glmS Ribozyme},
  number={51},
  volume={23},
  issn={0947-6539},
  journal={Chemistry - A European Journal},
  pages={12604--12612},
  author={Matzner, Daniel and Schüller, Anna and Seitz, Torben and Wittmann, Valentin and Mayer, Günter}
}
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