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 pharmaceuticals. The structures of glycosidase inhibitors can be categorized into two major classes; ground-state mimetics and transition-state mimetics. The former has a chair-shaped six-membered structure that mimics monosaccharides where ring oxygens are often replaced with other elements for an improved binding affinity. On the other hand, the latter possesses a somewhat distorted shape compared with the chair conformation of carbohydrates. One of the ways to derive such distortion is by the introduction of sp2 character into the six-membered ring, and another is by ring contraction to form a five-membered system for the transition-state mimetics. The functions of these transition-state mimetics are often unpredictable regarding inhibitory activity and enzyme specificity. This review focuses on such “difficult to predict” species in an attempt to extract information or common aspects for the future development of inhibitors of glycosidases based on transition-state mimetics.
Keywords: Glycosidase, inhibitor, azasugar, pyrrolidine, imino sugar, transition, conformational change
Rights & PermissionsPrintExport