Journal ArticleDOI
Generalized anomeric effect in action: synthesis and evaluation of stable reducing indolizidine glycomimetics as glycosidase inhibitors.
Víctor M. Díaz Pérez,M. Isabel Garcia Moreno,Carmen Ortiz Mellet,José Eduardo Fuentes,Juan C. Díaz Arribas,and F. Javier Cañada,José M. García Fernández +6 more
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TLDR
A series of aminoketalic castanospermine analogues incorporating a stereoelectronically anchored axial hydroxy group at the pseudoanomeric stereocenter (C-5) have been synthesized to satisfy the need for glucosidase inhibitors that are highly selective for alpha-glucosidases.Abstract:
A series of aminoketalic castanospermine analogues incorporating a stereoelectronically anchored axial hydroxy group at the pseudoanomeric stereocenter (C-5) have been synthesized to satisfy the need for glucosidase inhibitors that are highly selective for alpha-glucosidases. The polyhydroxylated bicyclic system was built from readily available hexofuranose derivatives through a synthetic scheme that involved (i) the construction of a five-membered cyclic (thio)carbamate or (thio)urea moiety at the nonreducing end and (ii) the intramolecular nucleophilic addition of the heterocyclic thiocarbamic nitrogen atom to the masked aldehyde group of the monosaccharide. A biological screening of the resulting reducing 2-oxa- and 2-azaindolizidines against several glycosidase enzymes is reported.read more
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Glycomimetic-based pharmacological chaperones for lysosomal storage disorders: lessons from Gaucher, GM1-gangliosidosis and Fabry diseases
TL;DR: The advancements made in this field in the last few years are reviewed and the future outlook through the lessons taught by three archetypical LSDs are reviewed: Gaucher disease, GM1-gangliosidosis and Fabry disease.
Journal ArticleDOI
Pharmacological chaperone therapy for Gaucher disease: a patent review.
TL;DR: This review summarizes the different approaches used to implement the concept of pharmacological chaperone therapy (PCT) for GD and discusses the relevant research, patents and patent applications filed in the last decade.
Journal ArticleDOI
Fullerene-sp2-Iminosugar Balls as Multimodal Ligands for Lectins and Glycosidases: A Mechanistic Hypothesis for the Inhibitory Multivalent Effect
Rocío Rísquez-Cuadro,José M. García Fernández,Jean-François Nierengarten,Carmen Ortiz Mellet +3 more
TL;DR: The data supports that: 1) multivalency allows modulating the affinity and selectivity of a given inhitope towards glycosidases; 2) multivalent presentation can switch on the inhibitory capacity for some inhitopes-glycosidase pairs, and 3) interactions of the multivalent inhibitors with non-glycone sites is critical for glycosdase recognition.
Journal ArticleDOI
Chaperone Activity of Bicyclic Nojirimycin Analogues for Gaucher Mutations in Comparison with N-(n-nonyl)Deoxynojirimycin
Zhuo Luan,Katsumi Higaki,Matilde Aguilar-Moncayo,Haruaki Ninomiya,Kousaku Ohno,M. Isabel García-Moreno,Carmen Ortiz Mellet,José M. García Fernández,Yoshiyuki Suzuki +8 more
TL;DR: The chaperone effects of the sp2 iminosugar were generally stronger than those observed for NN‐DNJ; this suggests that these compounds are promising candidates for clinical treatment of GD patients with a broad range of β‐Glu mutations, especially for neuronopathic forms of Gaucher disease.
Journal ArticleDOI
Synthesis of N-, S-, and C-glycoside castanospermine analogues with selective neutral α-glucosidase inhibitory activity as antitumour agents
Elena M. Sánchez-Fernández,Rocío Rísquez-Cuadro,Maud Chasseraud,Ahmed Ahidouch,Carmen Ortiz Mellet,Halima Ouadid-Ahidouch,José M. García Fernández +6 more
TL;DR: Evaluation in breast cancer cell growth indicated a significant antiproliferative potential that was dependent on the nature of the pseudoanomeric group.
References
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Über neue organische Phosphorverbindungen III. Phosphinmethylenderivate und Phosphinimine
Hermann Staudinger,Jules Meyer +1 more
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Sixty years of staudinger reaction
Journal ArticleDOI
Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.
Tom D. Heightman,Andrea Vasella +1 more
TL;DR: Not "from above", but "from the side": Configuration-retaining β-glycosidases protonate their substrate either anti or syn to the endocyclic C1-O bond as the first step in the enzymic cleavage of the glycosidic bond.
Journal ArticleDOI
Prevention of Lysosomal Storage in Tay-Sachs Mice Treated with N-Butyldeoxynojirimycin
Frances M. Platt,Gabrielle R. Neises,Gabriele Reinkensmeier,M J Townsend,V H Perry,Richard L. Proia,B Winchester,Raymond A. Dwek,T D Butters +8 more
TL;DR: Limiting the biosynthesis of the substrate (GM2) for the defective enzyme (beta-hexosaminidase A) prevents GSL accumulation and the neuropathology associated with its lysosomal storage.
Journal Article
Inhibitors of carbohydrate processing: A new class of anticancer agents.
TL;DR: The rationale for targeting Golgi carbohydrate processing pathways in the treatment of cancer, the preclinical and clinical results with swainsonine, and prospects for the development of second generation inhibitors with improved specificity for Golgi-processing enzymes are discussed.