title: 1-Deoxy-D-galactonojirimycins with dansyl capped N-substituents as β-galactosidase inhibitors and potential probes for GM1 gangliosidosis affected cell lines.
abstract: Two simple and reliably accessible intermediates, N-carboxypentyl- and N-aminohexyl-1-deoxy-D-galactonojirimycin were employed for the synthesis of a set of terminally N-dansyl substituted derivatives. Reaction of the terminal carboxylic acid of N-carboxypentyl-1-deoxy-D-galactonojirimycin with N-dansyl-1,6-diaminohexane provided the chain-extended fluorescent derivative. Employing bis(6-dansylaminohexyl)amine, the corresponding branched di-N-dansyl compound was obtained. Partially protected N-aminohexyl-1-deoxy-D-galactonojirimycin served as intermediate for two additional chain-extended fluorescent 1-deoxy-D-galactonojirimycin (1-DGJ) derivatives featuring terminal dansyl groups in the N-alkyl substituent. These new compounds are strong inhibitors of d-galactosidases and may serve as leads en route to pharmacological chaperones for GM1-gangliosidosis.
authors.affiliation: Carbohydrate Chemistry Team, Industrial Research Limited, PO Box 31-310, 5040 Lower Hutt, New Zealand.
authors.forename: Richard F G
authors.initials: RF
authors.lastname: Fröhlich
authors.forename: Richard H
authors.initials: RH
authors.lastname: Furneaux
authors.forename: Don J
authors.initials: DJ
authors.lastname: Mahuran
authors.forename: Robert
authors.initials: R
authors.lastname: Saf
authors.forename: Arnold E
authors.initials: AE
authors.lastname: Stütz
authors.forename: Michael B
authors.initials: MB
authors.lastname: Tropak
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Wicki
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Withers
authors.forename: Tanja M
authors.initials: TM
authors.lastname: Wrodnigg
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D002415:Cats; D002460:Cell Line; D003619:Dansyl Compounds / Q000737:chemistry*; D003959:Diamines / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000494:pharmacology; D016537:Gangliosidosis, GM1 / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D007097:Imines / Q000737:chemistry; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry / Q000494:pharmacology; D015335:Molecular Probes / Q000138:chemical synthesis / Q000494:pharmacology; D058990:Molecular Targeted Therapy; D010713:Phosphatidylcholines / Q000737:chemistry*; D010940:Plant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D013402:Sugar Alcohols / Q000737:chemistry; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: C486051:1-deoxy-D-galactohomonojirimycin; C496906:1-myristoyl-2-(12-((5-dimethylamino-1-naphthalenesulfonyl)amino)dodecanoyl)-sn-glycero-3-phosphocholine; D001426:Bacterial Proteins; D003619:Dansyl Compounds; D003959:Diamines; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007097:Imines; D018832:Molecular Chaperones; D015335:Molecular Probes; D010713:Phosphatidylcholines; D010940:Plant Proteins; D013402:Sugar Alcohols; D017485:1-Deoxynojirimycin; D001616:beta-Galactosidase; C007297:1,6-diaminohexane