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Rapid One-step Enzymatic Synthesis and All-aqueous Purification of Trehalose Analogues
Published on: February 17, 2017
Thiasugars: potential glycosidase inhibitors
Hideya Yuasa1, Masayuki Izumi, Hironobu Hashimoto
1Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midoriku, Yokohama, Japan. hyuasa@bio.titech.ac.jp
Current Topics in Medicinal Chemistry
|February 10, 2009
Summary
Synthetic thiasugars, carbohydrate analogs with sulfur in the ring, show potent glycosidase inhibition. Structure-activity studies reveal key interactions, leading to development of novel enzyme inhibitors.
Area of Science:
- Carbohydrate Chemistry
- Enzyme Inhibition
- Medicinal Chemistry
Background:
- Glycosidases are crucial enzymes involved in various biological processes.
- Synthetic carbohydrate analogs, particularly thiasugars, offer potential as enzyme inhibitors.
- Understanding structure-activity relationships is key to designing effective inhibitors.
Purpose of the Study:
- To survey the inhibitory activities of synthetic thiasugars against glycosidases.
- To investigate the structure-activity relationships of thiasugar-based inhibitors.
- To explore the potential of thiasugars in developing novel therapeutic agents.
Main Methods:
- Synthesis of various thiasugar analogs, including thiopyran and thiafuran structures.
- Enzyme inhibition assays to determine inhibitory constants (K(i) values).
- Structure-activity relationship (SAR) studies to elucidate binding interactions.
Main Results:
- 5-Thio-L-fucose demonstrated micromolar inhibition against a fucosidase, attributed to hydrophobic interactions.
- Oligosaccharide analogs incorporating thiasugars exhibited glycosidase resistance and lectin/antibody binding.
- A thiafuran-based sulfylimine showed weak glucosidase inhibition, while salacinol analogs revealed the importance of sulfonium ions and sulfate anions.
Conclusions:
- Synthetic thiasugars are promising scaffolds for developing potent glycosidase inhibitors.
- Specific structural features, like hydrophobic interactions and charged moieties, are critical for high inhibitory activity.
- Thiasugar analogs have potential applications in therapeutics and biochemical research.
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