title: Cardiac glycosides. 1. A systematic study of digitoxigenin D-glycosides.
abstract: A series of digitoxigenin glycosides was studied: five with beta-D-sugars varying stepwise in sugar structure from beta-D-digitoxose to beta-D-galactose, including one beta-D/alpha-D pair. I50 values for these glycosides and digitoxigenin were determined with hog kidney Na+, K+-ATPase. These data suggest a major and unexpected role for 4'-OH conformation in the sugar. All the glycosides with an equatorial 4'-OH were more active than the two with the 4'-OH axial [digitoxigenin beta-D-galactoside (6) I50 = 6.45 X 10(-8) M; digitoxigenin 2'-deoxy-alpha-D-ribo-hexopyranoside (alpha-3a) I50 = 9.33 X 10(-8) M; digitoxigenin I50 = 1.17 X 10(-7) M]. Stereochemistry of the 3'-OH had much less of an activity role than that of the 4'-OH, in contrast to existing models of "sugar-site" binding.
mesh_terms: D000818:Animals; D002236:Carbohydrate Conformation; D002301:Cardiac Glycosides / Q000032:analysis*; D003461:Crystallography; D004073:Digitoxigenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013552:Swine
chemical_list: D002301:Cardiac Glycosides; D004073:Digitoxigenin; C035486:digitoxigenin monodigitoxoside; C036592:digitoxigenin-galactose; D000254:Sodium-Potassium-Exchanging ATPase