104154-10-1Relevant academic research and scientific papers
1-Deoxynojirimycins with dansyl capped N-substituents as probes for Morbus Gaucher affected cell lines
Froehlich, Richard F. G.,Furneaux, Richard H.,Mahuran, Don J.,Rigat, Brigitte A.,Stuetz, Arnold E.,Tropak, Michael B.,Wicki, Jacqueline,Withers, Stephen G.,Wrodnigg, Tanja M.
, p. 1371 - 1376 (2010)
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 subinhibitory concentrations, the activity of β-glucocerebrosidase in a Gaucher fibroblast (N370S) cell-line through chaperoning of the enzyme to the lysosome.
Glycomimetic affinity-enrichment proteomics identifies partners for a clinically-utilized iminosugar
Cruz, Isa N.,Barry, Conor S.,Kramer, Holger B.,Chuang, C. Celeste,Lloyd, Sarah,Van Der Spoel, Aarnoud C.,Platt, Frances M.,Yang, Min,Davis, Benjamin G.
, p. 3442 - 3446 (2013)
Widescale evaluation of interacting partners for carbohydrates is an underexploited area. Probing of the 'glyco-interactome' has particular relevance given the lack of direct genetic control of glycoconjugate biosynthesis. Here we design, create and utilize a natural product-derived glycomimetic iminosugar probe in a Glycomimetic Affinity-enrichment Proteomics (Glyco-AeP) strategy to elucidate key interactions directly from mammalian tissue. The binding partners discovered here and the associated genomic analysis implicate a subset of chaperone and junctional proteins as important in male fertility. Such repurposing of existing therapeutics thus creates direct routes to probing in vivo function. The success of this strategy suggests a general approach to discovering 'carbohydrate-active' partners in biology.
1-Deoxy-d-galactonojirimycins with dansyl capped N-substituents as β-galactosidase inhibitors and potential probes for GM1 gangliosidosis affected cell lines
Fr?hlich, Richard F.G.,Furneaux, Richard H.,Mahuran, Don J.,Saf, Robert,Stütz, Arnold E.,Tropak, Michael B.,Wicki, Jacqueline,Withers, Stephen G.,Wrodnigg, Tanja M.
, p. 1592 - 1598 (2011)
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.
Synthetic 1-deoxynojirimycin N-substituted peptides offer prolonged disruption to N-linked glycan processing
Aguilar, Aim Lpez,Escribano, Jaime,Wentworth, Paul,Butters, Terry D.
, p. 2809 - 2813 (2015/02/02)
A panel of 1-deoxynojirimycin (DNJ) N-linked peptides were synthesized. Their IC50 values were measured in vitro against a-glucosidases I and II and were found to be in the micromolar range for both isozymes, and better than that of the iminosugar NB-DNJ (miglustat, 3) against a-glucosidase II. Cell-based studies revealed that although the free iminosugar 3 is most effective at disrupting N-linked glycan processing for shortterm incubations (one day), when the cell-based studies were extended to three days, the DNJ N-linked tetrapeptide KDEL, which is an endoplasmic reticulum (ER)-retaining sequence, performed far better than 3. In low inhibitor washout studies, NB-DNJ inhibition was decreased to zero after 24 h, but DNJ- KDEL retained 13% activity. This method offers a general approach for targeting drugs to the ER and prolonging their activity. Moreover, it is modular, so as new iminosugars of increased potency are discovered, they can be added to this template for targeting.
Synthesis and biological evaluation of novel biotin-iminoalditol conjugates
Pototschnig, Gerit,De Csaky, Christian Morales,Montenegro Burke, Jose R.,Schitter, Georg,Stuetz, Arnold E.,Tarling, Chris A.,Withers, Stephen G.,Wrodnigg, Tanja M.
supporting information; experimental part, p. 4077 - 4079 (2010/09/04)
Biotin-iminosugar conjugates of different configuration such as d-gluco, d-galacto, l-ido as well as a furanoid representative in the d-manno configuration have been synthesised and exhibit powerful inhibition of β-glucosidase from Agrobacterium sp. with Ki values in the range of the respective parent compounds. Such molecular probes have potential for activity-based protein profiling taking advantage of the biotin-(strept)avidin interaction.
Fluorous iminoalditols: A new family of glycosidase inhibitors and pharmacological chaperones
Schitter, Georg,Steiner, Andreas J.,Pototschnig, Gerit,Scheucher, Elisabeth,Thonhofer, Martin,Tarling, Chris A.,Withers, Stephen G.,Fantur, Katrin,Paschke, Eduard,Mahuran, Don J.,Rigat, Brigitte A.,Tropak, Michael B.,Illaszewicz, Carina,Saf, Robert,Stuetz, Arnold E.,Wrodnigg, Tanja M.
experimental part, p. 2026 - 2033 (2011/11/30)
A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring N-substituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasi
