1-Deoxynojirimycins with dansyl capped N-substituents as probes for Morbus Gaucher affected cell lines.
Cyclization by double reductive amination of d-xylo-hexos-5-ulose with methyl 6-aminohexanoate gave (methoxycarbonyl)pentyl-1-deoxynojirimycin. Reaction of the terminal carboxylic acid with N-dansyl-1,6-diaminohexane provided the corresponding chain-extended fluorescent derivative. By reaction with bis(6-dansylaminohexyl)amine, the corresponding branched di-N-dansyl compound was obtained. Both compounds are strong inhibitors of d-glucosidases and could also be shown to distinctly improve, at sub-inhibitory concentrations, the activity of beta-glucocerebrosidase in a Gaucher fibroblast (N370S) cell-line through chaperoning of the enzyme to the lysosome.
Fröhlich
Richard F G
RF
Carbohydrate Chemistry Team, Industrial Research Limited, PO Box 31-310, 5040 Lower Hutt, New Zealand.
Furneaux
Richard H
RH
Mahuran
Don J
DJ
Rigat
Brigitte A
BA
Stütz
Arnold E
AE
Tropak
Michael B
MB
Wicki
Jacqueline
J
Withers
Stephen G
SG
Wrodnigg
Tanja M
TM
D017485:1-Deoxynojirimycin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005347:Fibroblasts / Q000473:pathology; D005776:Gaucher Disease / Q000473:pathology*; D005959:Glucosidases / Q000037:antagonists & inhibitors; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D009584:Nitrogen / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D012231:Rhizobium / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000201:enzymology
C496906:1-myristoyl-2-(12-((5-dimethylamino-1-naphthalenesulfonyl)amino)dodecanoyl)-sn-glycero-3-phosphocholine; D004791:Enzyme Inhibitors; D010713:Phosphatidylcholines; D017485:1-Deoxynojirimycin; D005959:Glucosidases; D009584:Nitrogen
Carbohydr Res. 2007 Sep 3;342(12-13):1850-8
17442281
Chembiochem. 2009 Jun 15;10(9):1480-5
19437524
Biochemistry. 1992 Oct 20;31(41):9961-9
1390780
Angew Chem Int Ed Engl. 1999 Mar 15;38(6):750-770
29711789
J Biol Chem. 2009 Aug 28;284(35):23502-16
19578116
J Med Chem. 2007 Jan 11;50(1):94-100
17201413
Eur J Biochem. 1984 Jul 2;142(1):85-90
6235111
Angew Chem Int Ed Engl. 2005 Dec 1;44(45):7450-3
16231389
Bioorg Med Chem Lett. 2008 Mar 15;18(6):1922-5
18281216
J Org Chem. 2007 Feb 16;72(4):1088-97
17243712
Angew Chem Int Ed Engl. 2009;48(47):8848-69
19862781