The highly stereocontrolled de novo synthesis of l-NBDNJ (the unnatural enantiomer of the iminosugar drug Miglustat) and a preliminary evaluation of its chaperoning potential are herein reported. l-NBDNJ is able to enhance lysosomal α-glucosidase levels in Pompe disease fibroblasts, either when administered singularly or when coincubated with the recombinant human α-glucosidase. In addition, differently from its d-enantiomer, l-NBDNJ does not act as a glycosidase inhibitor.
J Med Chem
9462 - 9469
1-Deoxynojirimycin, Allosteric Regulation, Cell Line, Enzyme Activation, Enzyme Inhibitors, Fibroblasts, Glycogen Storage Disease Type II, Humans, Lysosomes, Models, Molecular, Stereoisomerism, alpha-Glucosidases