N-Butyl-l-deoxynojirimycin (l-NBDNJ): Synthesis of an Allosteric Enhancer of α-Glucosidase Activity for the Treatment of Pompe Disease.

D'Alonzo D., De Fenza M., Porto C., Iacono R., Huebecker M., Cobucci-Ponzano B., Priestman DA., Platt F., Parenti G., Moracci M., Palumbo G., Guaragna A.

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.

DOI

10.1021/acs.jmedchem.7b00646

Type

Journal

J Med Chem

Publication Date

14/12/2017

Volume

60

Pages

9462 - 9469

Keywords

1-Deoxynojirimycin, Allosteric Regulation, Cell Line, Enzyme Activation, Enzyme Inhibitors, Fibroblasts, Glycogen Storage Disease Type II, Humans, Lysosomes, Models, Molecular, Stereoisomerism, alpha-Glucosidases

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