title: [Sugar analog inhibitors for glycosidases, tools for the elucidation of enzymatic hydrolysis of glycosides].
abstract: Sugar derivatives with a basic group on C-1 (glycosylamines, 5-amino-5-deoxypyranoses, and 1,5-iminohexitols) are bound by most glycosidases 10(2)- to 10(5)-fold more tightly than their nonbasic counterparts. This high affinity and an up to 10(5)-fold better inhibition relative to hexoses by hexono-delta-lactones and lactams point to a catalytic mechanism characterized by a transition state with a partial positive charge and planar geometry at the anomeric carbon of the substrate. Protonation of the glycosidic oxygen atom and stabilization of the positive charge by a carboxylate group strongly shielded from the aqueous environment lower the free energy of activation to an extent which causes an up to 10(14)-fold rate acceleration relative to the nonenzymatic hydrolysis of glycosides.
authors.affiliation: Institut für Biochemie der Universität, Köln.
authors.forename: G
authors.initials: G
authors.lastname: Legler
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006868:Hydrolysis; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000378:metabolism
chemical_list: D002241:Carbohydrates; D004791:Enzyme Inhibitors; D011134:Polysaccharides; D006026:Glycoside Hydrolases