Current Topics in Medicinal Chemistry - Volume 9, Issue 1, 2009

Carbohydrates are used as nutrients, structural components and informational tags in life system and they are continuously synthesized, modified and degraded by numerous kinds of carbohydrate-related enzymes. The inhibitors of these enzymes, therefore, are commercial or potential medicines for diseases caused by upregulated or unwanted activities of these enzymes. Starch taken in the digestive system as a nutrie Read More

α-Glucosidase inhibitors are marketed as therapeutic drugs for diabetes that act through the inhibition of carbohydrate metabolism. Inhibitors of the α-glucosidases that are involved in the biosynthesis of N-linked oligosaccharide chains have been reported to have antitumor, antiviral, and apoptosis-inducing activities, and some have been used clinically. α-Glucosidase inhibitors have interesting biological activities, and their Read More

Glycosidases mediate the digestion of oligosaccharides in the small intestine as well as the processing of cell surface oligosaccharides, which play important roles in cell to cell recognition during infections, metastasis, and immune responses. Thus, agents that control the activities of glycosidases could have therapeutic effects against many carbohydrate-related diseases. In fact, many fruitful efforts have been made t Read More

Glycosidases are involved in various important biological processes including digestion of starch in the intestine, oligosaccharide processing inside rough ER and Golgi apparatus, and degradation of glycoconjugates in lysosomes. It is apparent that inhibitors of this class of enzymes are useful in the investigation of biological functions of glycoconjugates. Furthermore, it is believed that these compounds are important as pharmac Read More

5a-Carba-α-D-glucopyranosylamine, validamine, and analogous compounds valienamine and valiolamine, have proved to be important lead compounds for development of clinically useful medicines, including the very strong α- glucosidase inhibitor, voglibose, N-(1,3-dihydroxyprop-2-yl)valiolamine, now used widely as a clinically important antidiabetic agent. In this review, we describe recent advances in development Read More

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 Ki 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 hydroph Read More

Oligosaccharides in glycoconjugates such as glycoproteins and glycolipids play important roles in a variety of biological functions. Since glycosyltransferases are responsible for the biosynthesis of these oligosaccharides, inhibitors of glycosyltransferases are targets for drug discovery. Bisubstrate analogues, in which donor and acceptor analogue are covalently attached to each other, offer donor's high affinity and acce Read More

Recent structural and kinetic studies indicated that enzymes shift their peripheral structures of the catalytic sites dynamically to modify the substrate structures. Molecules which disturb such mechanism of specific enzymes may become potent candidates for therapeutic reagent. This article describes a versatile strategy to synthesize new class of mechanism-based inhibitors for glycosyltransferases and glycoside hydro Read More

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