Azasugar inhibitors as pharmacological chaperones for Krabbe disease

Hill, Chris H.; Viuff, Agnete H.; Spratley, Samantha J.; Salamone, Stéphane; Christensen, Stig H.; Read, Randy J.; Moriarty, Nigel W.; Jensen, Henrik H.; Deane, Janet E.

doi:10.1039/C5SC00754B

Title: Azasugar inhibitors as pharmacological chaperones for Krabbe disease

Journal Article · Mon Mar 23 00:00:00 EDT 2015 · Chemical Science

DOI:https://doi.org/10.1039/C5SC00754B· OSTI ID:1214555

Hill, Chris H. ^[1]; Viuff, Agnete H. ^[2]; Spratley, Samantha J. ^[1]; Salamone, Stéphane ^[2]; Christensen, Stig H. ^[2]; Read, Randy J. ^[1]; Moriarty, Nigel W. ^[3]; Jensen, Henrik H. ^[2]; Deane, Janet E. ^[1]

Univ. of Cambridge, Cambridge (United Kingdom)
Aarhus Univ., Aarhus (Denmark)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231; 082961/Z/07/Z; 100140; UF100371

OSTI ID:: 1214555

Journal Information:: Chemical Science, Vol. 6, Issue 5; ISSN 2041-6520

Publisher:: Royal Society of ChemistryCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 38 works

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References (82)

The plasma activities of lysosomal enzymes in infants with necrotizing enterocolitis: New promising class of biomarkers? Benkoe, Thomas M.; Mechtler, Thomas P.; Pones, Mario Clinica Chimica Acta, Vol. 438 https://doi.org/10.1016/j.cca.2014.08.043	journal	January 2015
Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB Ficko-Blean, E.; Stubbs, K. A.; Nemirovsky, O. Proceedings of the National Academy of Sciences, Vol. 105, Issue 18 https://doi.org/10.1073/pnas.0711491105	journal	April 2008
The pharmacokinetics and tissue distribution of the glucosylceramide synthase inhibitor miglustat in the rat Treiber, A.; Morand, O.; Clozel, M. Xenobiotica, Vol. 37, Issue 3 https://doi.org/10.1080/00498250601094543	journal	March 2007
Krabbe leukodystrophy in a selected population with high rate of late onset forms: longer survival linked to c.121G>A (p.Gly41Ser) mutation Fiumara, A.; Barone, R.; Arena, A. Clinical Genetics, Vol. 80, Issue 5 https://doi.org/10.1111/j.1399-0004.2010.01572.x	journal	November 2010
Molecular Characterization of Mutations That Cause Globoid Cell Leukodystrophy and Pharmacological Rescue Using Small Molecule Chemical Chaperones Lee, W. C.; Kang, D.; Causevic, E. Journal of Neuroscience, Vol. 30, Issue 16 https://doi.org/10.1523/JNEUROSCI.6383-09.2010	journal	April 2010
A high-throughput screening assay using Krabbe disease patient cells Ribbens, Jameson; Whiteley, Grace; Furuya, Hirokazu Analytical Biochemistry, Vol. 434, Issue 1 https://doi.org/10.1016/j.ab.2012.10.034	journal	March 2013
Chemoenzymatic Synthesis of Isogalactofagomine Liang, Xifu; Lohse, Anders; Bols, Mikael The Journal of Organic Chemistry, Vol. 65, Issue 22 https://doi.org/10.1021/jo000699r	journal	November 2000
Insights into Krabbe disease from structures of galactocerebrosidase Deane, J. E.; Graham, S. C.; Kim, N. N. Proceedings of the National Academy of Sciences, Vol. 108, Issue 37 https://doi.org/10.1073/pnas.1105639108	journal	August 2011
Chemically modified -glucuronidase crosses blood-brain barrier and clears neuronal storage in murine mucopolysaccharidosis VII Grubb, J. H.; Vogler, C.; Levy, B. Proceedings of the National Academy of Sciences, Vol. 105, Issue 7 https://doi.org/10.1073/pnas.0712147105	journal	February 2008
Isogalactofagomine lactam. A neutral nanomolar galactosidase inhibitor Søhoel, Helmer; Liang, Xifu; Bols, Mikael Journal of the Chemical Society, Perkin Transactions 1, Issue 14 https://doi.org/10.1039/b103831c	journal	January 2001
Synthesis of 1-azagalactofagomine, a potent galactosidase inhibitor Jensen, Henrik Helligsø; Bols, Mikael Journal of the Chemical Society, Perkin Transactions 1, Issue 8 https://doi.org/10.1039/b007973l	journal	January 2001
Synthesis of N-alkylated noeurostegines and evaluation of their potential as treatment for Gaucher’s disease Rasmussen, Tina S.; Allman, Sarah; Twigg, Gabriele Bioorganic & Medicinal Chemistry Letters, Vol. 21, Issue 5 https://doi.org/10.1016/j.bmcl.2010.12.106	journal	March 2011
Ex Vivo and in Vivo Effects of Isofagomine on Acid β-Glucosidase Variants and Substrate Levels in Gaucher Disease Sun, Ying; Liou, Benjamin; Xu, You-Hai Journal of Biological Chemistry, Vol. 287, Issue 6 https://doi.org/10.1074/jbc.M111.280016	journal	December 2011
Towards automated crystallographic structure refinement with phenix.refine Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4 https://doi.org/10.1107/S0907444912001308	journal	March 2012
The pharmacological chaperone 1-deoxygalactonojirimycin increases α-galactosidase A levels in Fabry patient cell lines Benjamin, E. R.; Flanagan, J. J.; Schilling, A. Journal of Inherited Metabolic Disease, Vol. 32, Issue 3 https://doi.org/10.1007/s10545-009-1077-0	journal	April 2009
Stereoelectronic Substituent Effects in Polyhydroxylated Piperidines and Hexahydropyridazines Jensen, Henrik Helligsø; Lyngbye, Laila; Jensen, Astrid Chemistry - A European Journal, Vol. 8, Issue 5 https://doi.org/10.1002/1521-3765(20020301)8:5<1218::AID-CHEM1218>3.0.CO;2-X	journal	March 2002
Hematopoietic Stem-Cell Transplantation in Globoid-Cell Leukodystrophy Krivit, William; Shapiro, Elsa G.; Peters, Charles New England Journal of Medicine, Vol. 338, Issue 16 https://doi.org/10.1056/NEJM199804163381605	journal	April 1998
How good are my data and what is the resolution? Evans, Philip R.; Murshudov, Garib N. Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7 https://doi.org/10.1107/S0907444913000061	journal	June 2013
Bone marrow transplantation increases efficacy of central nervous system-directed enzyme replacement therapy in the murine model of globoid cell leukodystrophy Qin, Elizabeth Y.; Hawkins-Salsbury, Jacqueline A.; Jiang, Xuntian Molecular Genetics and Metabolism, Vol. 107, Issue 1-2 https://doi.org/10.1016/j.ymgme.2012.05.021	journal	September 2012
Recent Developments of Transition-State Analogue Glycosidase Inhibitors of Non-Natural Product Origin Lillelund, Vinni H.; Jensen, Henrik H.; Liang, Xifu Chemical Reviews, Vol. 102, Issue 2 https://doi.org/10.1021/cr000433k	journal	February 2002
Asymmetric Organocatalytic Electrophilic Phosphination Nielsen, Martin; Jacobsen, Christian Borch; Jørgensen, Karl Anker Angewandte Chemie International Edition, Vol. 50, Issue 14 https://doi.org/10.1002/anie.201007188	journal	February 2011
5-Trihydroxypropyl-dihydrouracil derivatives as precursors of 1-azasugars: application to the stereoselective synthesis of d-galacto-isofagomine Spanu, Pietro; Candia, Cristina de; Ulgheri, Fausta Tetrahedron Letters, Vol. 51, Issue 18 https://doi.org/10.1016/j.tetlet.2010.02.093	journal	May 2010
Iminosugars past, present and future: medicines for tomorrow Horne, Graeme; Wilson, Francis X.; Tinsley, Jon Drug Discovery Today, Vol. 16, Issue 3-4 https://doi.org/10.1016/j.drudis.2010.08.017	journal	February 2011
Promising results of the chaperone effect caused by iminosugars and aminocyclitol derivatives on mutant glucocerebrosidases causing Gaucher disease Sánchez-Ollé, Gessamí; Duque, Joana; Egido-Gabás, Meritxell Blood Cells, Molecules, and Diseases, Vol. 42, Issue 2 https://doi.org/10.1016/j.bcmd.2008.11.002	journal	March 2009
electronic Ligand Builder and Optimization Workbench ( eLBOW ): a tool for ligand coordinate and restraint generation Moriarty, Nigel W.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 10 https://doi.org/10.1107/S0907444909029436	journal	September 2009
Delivery of endocytosed membrane proteins to the lysosome Pryor, Paul R.; Luzio, J. Paul Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1793, Issue 4 https://doi.org/10.1016/j.bbamcr.2008.12.022	journal	April 2009
A Chaperone Enhances Blood α-Glucosidase Activity in Pompe Disease Patients Treated With Enzyme Replacement Therapy Parenti, Giancarlo; Fecarotta, Simona; la Marca, Giancarlo Molecular Therapy, Vol. 22, Issue 11 https://doi.org/10.1038/mt.2014.138	journal	November 2014
Crystal Structures of Complexes of N -Butyl- and N -Nonyl-Deoxynojirimycin Bound to Acid β-Glucosidase : INSIGHTS INTO THE MECHANISM OF CHEMICAL CHAPERONE ACTION IN GAUCHER DISEASE Brumshtein, Boris; Greenblatt, Harry M.; Butters, Terry D. Journal of Biological Chemistry, Vol. 282, Issue 39 https://doi.org/10.1074/jbc.M705005200	journal	July 2007
In vitro inhibition and intracellular enhancement of lysosomal α-galactosidase A activity in Fabry lymphoblasts by 1-deoxygalactonojirimycin and its derivatives : Enhancement of α-Gal A in Fabry lymphoblasts Asano, Naoki; Ishii, Satoshi; Kizu, Haruhisa European Journal of Biochemistry, Vol. 267, Issue 13 https://doi.org/10.1046/j.1432-1327.2000.01457.x	journal	July 2000
The Pharmacological Chaperone N-butyldeoxynojirimycin Enhances Enzyme Replacement Therapy in Pompe Disease Fibroblasts Porto, Caterina; Cardone, Monica; Fontana, Federica Molecular Therapy, Vol. 17, Issue 6 https://doi.org/10.1038/mt.2009.53	journal	June 2009
Isofagomine increases lysosomal delivery of exogenous glucocerebrosidase Shen, Jin-Song; Edwards, Nancy J.; Hong, Young Bin Biochemical and Biophysical Research Communications, Vol. 369, Issue 4 https://doi.org/10.1016/j.bbrc.2008.02.125	journal	May 2008
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
LigPlot+: Multiple Ligand–Protein Interaction Diagrams for Drug Discovery Laskowski, Roman A.; Swindells, Mark B. Journal of Chemical Information and Modeling, Vol. 51, Issue 10 https://doi.org/10.1021/ci200227u	journal	October 2011
Correlation between enzyme activity and substrate storage in a cell culture model system for Gaucher disease Schueler, U. H.; Kolter, T.; Kaneski, C. R. Journal of Inherited Metabolic Disease, Vol. 27, Issue 5 https://doi.org/10.1023/B:BOLI.0000042959.44318.7c	journal	January 2004
GALC Deletions Increase the Risk of Primary Open-Angle Glaucoma: The Role of Mendelian Variants in Complex Disease Liu, Yutao; Gibson, Jason; Wheeler, Joshua PLoS ONE, Vol. 6, Issue 11 https://doi.org/10.1371/journal.pone.0027134	journal	November 2011
Lysosomal Storage Diseases: From Pathophysiology to Therapy Parenti, Giancarlo; Andria, Generoso; Ballabio, Andrea Annual Review of Medicine, Vol. 66, Issue 1 https://doi.org/10.1146/annurev-med-122313-085916	journal	January 2015
An extremely potent inhibitor for β-galactosidase Ichikawa, Yoshitaka; Igarashi, Yasuhiro Tetrahedron Letters, Vol. 36, Issue 26 https://doi.org/10.1016/0040-4039(95)00870-I	journal	June 1995
A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease Rafi, Mohammad A.; Luzi, Paola; Chen, Yue Qun Human Molecular Genetics, Vol. 4, Issue 8 https://doi.org/10.1093/hmg/4.8.1285	journal	January 1995
Asymmetric Synthesis of All Stereoisomers of Isofagomine Using [2,3]-Wittig Rearrangement Takahata, Hiroki; Mihara, Yukiko; Ojima, Hidetomo HETEROCYCLES, Vol. 72, Issue 1 https://doi.org/10.3987/COM-07-S(K)58	journal	January 2007
Enzyme Replacement for Lysosomal Diseases Brady, Roscoe O. Annual Review of Medicine, Vol. 57, Issue 1 https://doi.org/10.1146/annurev.med.57.110104.115650	journal	February 2006
Cellular effects of deoxynojirimycin analogues: uptake, retention and inhibition of glycosphingolipid biosynthesis Mellor, Howard R.; Neville, David C. A.; Harvey, David J. Biochemical Journal, Vol. 381, Issue 3 https://doi.org/10.1042/BJ20031822	journal	July 2004
Targeting of the CNS in MPS-IH Using a Nonviral Transferrin-α-l-iduronidase Fusion Gene Product Osborn, Mark J.; McElmurry, Ron T.; Peacock, Brandon Molecular Therapy, Vol. 16, Issue 8 https://doi.org/10.1038/mt.2008.119	journal	August 2008
FEM: Feature Enhanced Map Afonine, Pavel Acta Crystallographica Section A Foundations and Advances, Vol. 70, Issue a1 https://doi.org/10.1107/S2053273314096818	journal	August 2014
The galactocerebrosidase enzyme contributes to the maintenance of a functional hematopoietic stem cell niche Visigalli, Ilaria; Ungari, Silvia; Martino, Sabata Blood, Vol. 116, Issue 11 https://doi.org/10.1182/blood-2009-12-256461	journal	September 2010
Molecular heterogeneity of Krabbe disease Fu, L.; Inui, K.; Nishigaki, T. Journal of Inherited Metabolic Disease, Vol. 22, Issue 2, p. 155-162 https://doi.org/10.1023/A:1005449919660	journal	April 1999
Two different mutations are responsible for Krabbe disease in the Druze and Moslem Arab populations in Israel Rafi, Mohammad A.; Luzi, Paola; Zlotogora, Joel Human Genetics, Vol. 97, Issue 3 https://doi.org/10.1007/BF02185759	journal	March 1996
Immune Response to Enzyme Replacement Therapy in Lysosomal Storage Disorder Patients and Animal Models Brooks, Doug A. Molecular Genetics and Metabolism, Vol. 68, Issue 2 https://doi.org/10.1006/mgme.1999.2894	journal	October 1999
The Phenix software for automated determination of macromolecular structures Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Methods, Vol. 55, Issue 1 https://doi.org/10.1016/j.ymeth.2011.07.005	journal	September 2011
Krabbe's Disease: Globoid Cell Type of Leukodystrophy D'Agostino, Anthony N. Archives of Neurology, Vol. 8, Issue 1 https://doi.org/10.1001/archneur.1963.00460010098012	journal	January 1963
xia2 : an expert system for macromolecular crystallography data reduction Winter, G. Journal of Applied Crystallography, Vol. 43, Issue 1 https://doi.org/10.1107/S0021889809045701	journal	December 2009
Microwave-assisted synthesis of pyrrolidine derivatives Chang, Yuan-Chun; Chir, Jiun-Ly; Tsai, Shuan-Yi Tetrahedron Letters, Vol. 50, Issue 34 https://doi.org/10.1016/j.tetlet.2009.06.062	journal	August 2009
Molecular genetics of Krabbe disease (globoid cell leukodystrophy): Diagnostic and clinical implications Wenger, David A.; Rafi, Mohammad A.; Luzi, Paola Human Mutation, Vol. 10, Issue 4 https://doi.org/10.1002/(SICI)1098-1004(1997)10:4<268::AID-HUMU2>3.0.CO;2-D	journal	January 1997
General atomic and molecular electronic structure system Schmidt, Michael W.; Baldridge, Kim K.; Boatz, Jerry A. Journal of Computational Chemistry, Vol. 14, Issue 11, p. 1347-1363 https://doi.org/10.1002/jcc.540141112	journal	November 1993
Dividing Cells Regulate Their Lipid Composition and Localization Atilla-Gokcumen, G. Ekin; Muro, Eleonora; Relat-Goberna, Josep Cell, Vol. 156, Issue 3 https://doi.org/10.1016/j.cell.2013.12.015	journal	January 2014
Using pharmacological chaperones to restore proteostasis Wang, Ya-Juan; Di, Xiao-Jing; Mu, Ting-Wei Pharmacological Research, Vol. 83 https://doi.org/10.1016/j.phrs.2014.04.002	journal	May 2014
Nrf2, a multi-organ protector? Lee, Jong-Min; Li, Jiang; Johnson, Delinda A. The FASEB Journal, Vol. 19, Issue 9 https://doi.org/10.1096/fj.04-2591hyp	journal	July 2005
Structures and mechanisms of glycosyl hydrolases Davies, Gideon; Henrissat, Bernard Structure, Vol. 3, Issue 9 https://doi.org/10.1016/S0969-2126(01)00220-9	journal	September 1995
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells: Galactocerebrosidase in Cancer Cells Beier, Ulf Henning; Görögh, Tibor International Journal of Cancer, Vol. 115, Issue 1 https://doi.org/10.1002/ijc.20851	journal	January 2005
Structure of acid β-glucosidase with pharmacological chaperone provides insight into Gaucher disease Lieberman, Raquel L.; Wustman, Brandon A.; Huertas, Pedro Nature Chemical Biology, Vol. 3, Issue 2 https://doi.org/10.1038/nchembio850	journal	December 2006
Structural snapshots illustrate the catalytic cycle of -galactocerebrosidase, the defective enzyme in Krabbe disease Hill, C. H.; Graham, S. C.; Read, R. J. Proceedings of the National Academy of Sciences, Vol. 110, Issue 51 https://doi.org/10.1073/pnas.1311990110	journal	December 2013
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
A New Route to Diverse 1-Azasugars from N -Boc-5-hydroxy-3-piperidene as a Common Building Block Ouchi, Hidekazu; Mihara, Yukiko; Takahata, Hiroki The Journal of Organic Chemistry, Vol. 70, Issue 13 https://doi.org/10.1021/jo050519j	journal	June 2005
A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo Yuzwa, Scott A.; Macauley, Matthew S.; Heinonen, Julia E. Nature Chemical Biology, Vol. 4, Issue 8 https://doi.org/10.1038/nchembio.96	journal	June 2008
Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors, 1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-d-mannitol: Syntheses and glucosidase-inhibitory activities of 1,2,5-trideoxy-2-fluoro-1,5-imino-d-glucitol and of 1,2,5-trideoxy-1-fluoro-2,5-imino-d-mannitol Andersen, Sören M.; Ebner, Michael; Ekhart, Christian W. Carbohydrate Research, Vol. 301, Issue 3-4 https://doi.org/10.1016/S0008-6215(97)00099-2	journal	June 1997
Pathology and Current Treatment of Neurodegenerative Sphingolipidoses Eckhardt, Matthias NeuroMolecular Medicine, Vol. 12, Issue 4 https://doi.org/10.1007/s12017-010-8133-7	journal	August 2010
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
1-Azafagomine: A Hydroxyhexahydropyridazine That Potently Inhibits Enzymatic Glycoside Cleavage Bols, Mikael; Hazell, Rita G.; Thomsen, Ib B. Chemistry - A European Journal, Vol. 3, Issue 6 https://doi.org/10.1002/chem.19970030616	journal	June 1997
Pharmacological chaperoning: A primer on mechanism and pharmacology Leidenheimer, Nancy J.; Ryder, Katelyn G. Pharmacological Research, Vol. 83 https://doi.org/10.1016/j.phrs.2014.01.005	journal	May 2014
A single mutation in the GALC gene is responsible for the majority of late onset Krabbe disease patients in the Catania (Sicily, Italy) region Lissens, Willy; Arena, Alessia; Seneca, Sara Human Mutation, Vol. 28, Issue 7 https://doi.org/10.1002/humu.9500	journal	January 2007
Mannose-6-phosphate pathway: A review on its role in lysosomal function and dysfunction Coutinho, Maria Francisca; Prata, Maria João; Alves, Sandra Molecular Genetics and Metabolism, Vol. 105, Issue 4 https://doi.org/10.1016/j.ymgme.2011.12.012	journal	April 2012
Treating lysosomal storage diseases with pharmacological chaperones: from concept to clinics Parenti, Giancarlo EMBO Molecular Medicine, Vol. 1, Issue 5 https://doi.org/10.1002/emmm.200900036	journal	August 2009
Pharmacological chaperones increase residual β-galactocerebrosidase activity in fibroblasts from Krabbe patients Berardi, Anna Sara; Pannuzzo, Giovanna; Graziano, Adriana Molecular Genetics and Metabolism, Vol. 112, Issue 4 https://doi.org/10.1016/j.ymgme.2014.05.009	journal	August 2014
The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability Niesen, Frank H.; Berglund, Helena; Vedadi, Masoud Nature Protocols, Vol. 2, Issue 9 https://doi.org/10.1038/nprot.2007.321	journal	September 2007
Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients Furuya, H.; Kukita, Yoh-ji; Nagano, Sukehisa Human Genetics, Vol. 100, Issue 3-4 https://doi.org/10.1007/s004390050532	journal	August 1997
Aza-Claisen rearrangement of 2-C-hydroxymethyl glycals as a versatile strategy towards synthesis of isofagomine and related biologically important azasugars Reddy, Y. Suman; Kancharla, Pavan K.; Roy, Rashmi Organic & Biomolecular Chemistry, Vol. 10, Issue 14 https://doi.org/10.1039/c2ob06851f	journal	January 2012
Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype–phenotype correlation Xu, Chengzhe; Sakai, Norio; Taniike, Masako Journal of Human Genetics, Vol. 51, Issue 6 https://doi.org/10.1007/s10038-006-0396-3	journal	April 2006
Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease Tappino, Barbara; Biancheri, Roberta; Mort, Matthew Human Mutation, Vol. 31, Issue 12 https://doi.org/10.1002/humu.21367	journal	September 2010
Retroviral Vector-Mediated Transfer of the Galactocerebrosidase (GALC) cDNA Leads to Overexpression and Transfer of GALC Activity to Neighboring Cells Rafi, Mohammad A.; Fugaro, Joseph; Amini, Shohreh Biochemical and Molecular Medicine, Vol. 58, Issue 2 https://doi.org/10.1006/bmme.1996.0042	journal	August 1996
A Role for Protein Misfolding in Immunogenicity of Biopharmaceuticals Maas, Coen; Hermeling, Suzanne; Bouma, Barend Journal of Biological Chemistry, Vol. 282, Issue 4 https://doi.org/10.1074/jbc.M605984200	journal	November 2006
E NZYME T HERAPY FOR L YSOSOMAL S TORAGE D ISEASE : Principles, Practice, and Prospects Grabowski, Gregory A.; Hopkin, Robert J. Annual Review of Genomics and Human Genetics, Vol. 4, Issue 1 https://doi.org/10.1146/annurev.genom.4.070802.110415	journal	September 2003
Iminosugar-Based Galactoside Mimics as Inhibitors of Galactocerebrosidase: SAR Studies and Comparison with Other Lysosomal Galactosidases Biela-Banaś, Anna; Oulaïdi, Farah; Front, Sophie ChemMedChem, Vol. 9, Issue 12 https://doi.org/10.1002/cmdc.201402411	journal	November 2014

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