Thiasugars: potential glycosidase inhibitors.

The inhibitory activities against glycosidases of synthetic thiasugars, the ring sulfur analogs of carbohydrate, were surveyed with a special emphasis on our own studies. 5-Thio-L-fucose, the ring sulfur analog of L-fucose, was the first thiopyran that shows a K(i) value in the micromolar range against a glycosidase. The structure-activity relationship studies for the fucosidase inhibition by 5-thio-L-fucose disclosed that a hydrophobic interaction between the ring sulfur atom and the enzyme is responsible for the strong binding. The syntheses and activities of di- and trisaccharide analogs incorporating thiasugars are also outlined. These oligosaccharide analogs are glycosidase-resistant and some of them show strong binding to antibodies or lectins. We created a sulfylimine compound having a thiafuran structure as a transition-state analog inhibitor of glucosidases and found that it has a weak inhibition against a glucosidase. The same thiafuran structure could be found in a natural product, salacinol, which was isolated and elucidated to be a strong glucosidase inhibitor by another group. A study of the structure-activity relationship using the synthetic analogs of salacinol indicated the relevance of both the sulfonium ion in the thiafuran ring and its intramolecular counter anion, sulfate, to the inhibition activity.