Azasugar inhibitors as pharmacological chaperones for Krabbe disease
Abstract
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 diseasemore »
- Authors:
-
- Univ. of Cambridge, Cambridge (United Kingdom)
- Aarhus Univ., Aarhus (Denmark)
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1214555
- Grant/Contract Number:
- AC02-05CH11231; 082961/Z/07/Z; 100140; UF100371
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Chemical Science
- Additional Journal Information:
- Journal Volume: 6; Journal Issue: 5; Journal ID: ISSN 2041-6520
- Publisher:
- Royal Society of Chemistry
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Hill, Chris H., Viuff, Agnete H., Spratley, Samantha J., Salamone, Stéphane, Christensen, Stig H., Read, Randy J., Moriarty, Nigel W., Jensen, Henrik H., and Deane, Janet E. Azasugar inhibitors as pharmacological chaperones for Krabbe disease. United States: N. p., 2015.
Web. doi:10.1039/C5SC00754B.
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. Azasugar inhibitors as pharmacological chaperones for Krabbe disease. United States. https://doi.org/10.1039/C5SC00754B
Hill, Chris H., Viuff, Agnete H., Spratley, Samantha J., Salamone, Stéphane, Christensen, Stig H., Read, Randy J., Moriarty, Nigel W., Jensen, Henrik H., and Deane, Janet E. Mon .
"Azasugar inhibitors as pharmacological chaperones for Krabbe disease". United States. https://doi.org/10.1039/C5SC00754B. https://www.osti.gov/servlets/purl/1214555.
@article{osti_1214555,
title = {Azasugar inhibitors as pharmacological chaperones for Krabbe disease},
author = {Hill, Chris H. and Viuff, Agnete H. and Spratley, Samantha J. and Salamone, Stéphane and Christensen, Stig H. and Read, Randy J. and Moriarty, Nigel W. and Jensen, Henrik H. and Deane, Janet E.},
abstractNote = {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.},
doi = {10.1039/C5SC00754B},
journal = {Chemical Science},
number = 5,
volume = 6,
place = {United States},
year = {Mon Mar 23 00:00:00 EDT 2015},
month = {Mon Mar 23 00:00:00 EDT 2015}
}
Web of Science
Works referenced in this record:
The plasma activities of lysosomal enzymes in infants with necrotizing enterocolitis: New promising class of biomarkers?
journal, January 2015
- Benkoe, Thomas M.; Mechtler, Thomas P.; Pones, Mario
- Clinica Chimica Acta, Vol. 438
Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB
journal, April 2008
- Ficko-Blean, E.; Stubbs, K. A.; Nemirovsky, O.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 18
The pharmacokinetics and tissue distribution of the glucosylceramide synthase inhibitor miglustat in the rat
journal, March 2007
- Treiber, A.; Morand, O.; Clozel, M.
- Xenobiotica, Vol. 37, Issue 3
Krabbe leukodystrophy in a selected population with high rate of late onset forms: longer survival linked to c.121G>A (p.Gly41Ser) mutation
journal, November 2010
- Fiumara, A.; Barone, R.; Arena, A.
- Clinical Genetics, Vol. 80, Issue 5
Molecular Characterization of Mutations That Cause Globoid Cell Leukodystrophy and Pharmacological Rescue Using Small Molecule Chemical Chaperones
journal, April 2010
- Lee, W. C.; Kang, D.; Causevic, E.
- Journal of Neuroscience, Vol. 30, Issue 16
A high-throughput screening assay using Krabbe disease patient cells
journal, March 2013
- Ribbens, Jameson; Whiteley, Grace; Furuya, Hirokazu
- Analytical Biochemistry, Vol. 434, Issue 1
Chemoenzymatic Synthesis of Isogalactofagomine
journal, November 2000
- Liang, Xifu; Lohse, Anders; Bols, Mikael
- The Journal of Organic Chemistry, Vol. 65, Issue 22
Insights into Krabbe disease from structures of galactocerebrosidase
journal, August 2011
- Deane, J. E.; Graham, S. C.; Kim, N. N.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 37
Chemically modified -glucuronidase crosses blood-brain barrier and clears neuronal storage in murine mucopolysaccharidosis VII
journal, February 2008
- Grubb, J. H.; Vogler, C.; Levy, B.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 7
Isogalactofagomine lactam. A neutral nanomolar galactosidase inhibitor
journal, January 2001
- Søhoel, Helmer; Liang, Xifu; Bols, Mikael
- Journal of the Chemical Society, Perkin Transactions 1, Issue 14
Synthesis of 1-azagalactofagomine, a potent galactosidase inhibitor
journal, January 2001
- Jensen, Henrik Helligsø; Bols, Mikael
- Journal of the Chemical Society, Perkin Transactions 1, Issue 8
Synthesis of N-alkylated noeurostegines and evaluation of their potential as treatment for Gaucher’s disease
journal, March 2011
- Rasmussen, Tina S.; Allman, Sarah; Twigg, Gabriele
- Bioorganic & Medicinal Chemistry Letters, Vol. 21, Issue 5
Ex Vivo and in Vivo Effects of Isofagomine on Acid β-Glucosidase Variants and Substrate Levels in Gaucher Disease
journal, December 2011
- Sun, Ying; Liou, Benjamin; Xu, You-Hai
- Journal of Biological Chemistry, Vol. 287, Issue 6
Towards automated crystallographic structure refinement with phenix.refine
journal, March 2012
- Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel
- Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4
The pharmacological chaperone 1-deoxygalactonojirimycin increases α-galactosidase A levels in Fabry patient cell lines
journal, April 2009
- Benjamin, E. R.; Flanagan, J. J.; Schilling, A.
- Journal of Inherited Metabolic Disease, Vol. 32, Issue 3
Stereoelectronic Substituent Effects in Polyhydroxylated Piperidines and Hexahydropyridazines
journal, March 2002
- Jensen, Henrik Helligsø; Lyngbye, Laila; Jensen, Astrid
- Chemistry - A European Journal, Vol. 8, Issue 5
Hematopoietic Stem-Cell Transplantation in Globoid-Cell Leukodystrophy
journal, April 1998
- Krivit, William; Shapiro, Elsa G.; Peters, Charles
- New England Journal of Medicine, Vol. 338, Issue 16
How good are my data and what is the resolution?
journal, June 2013
- Evans, Philip R.; Murshudov, Garib N.
- Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7
Bone marrow transplantation increases efficacy of central nervous system-directed enzyme replacement therapy in the murine model of globoid cell leukodystrophy
journal, September 2012
- Qin, Elizabeth Y.; Hawkins-Salsbury, Jacqueline A.; Jiang, Xuntian
- Molecular Genetics and Metabolism, Vol. 107, Issue 1-2
Recent Developments of Transition-State Analogue Glycosidase Inhibitors of Non-Natural Product Origin
journal, February 2002
- Lillelund, Vinni H.; Jensen, Henrik H.; Liang, Xifu
- Chemical Reviews, Vol. 102, Issue 2
Asymmetric Organocatalytic Electrophilic Phosphination
journal, February 2011
- Nielsen, Martin; Jacobsen, Christian Borch; Jørgensen, Karl Anker
- Angewandte Chemie International Edition, Vol. 50, Issue 14
5-Trihydroxypropyl-dihydrouracil derivatives as precursors of 1-azasugars: application to the stereoselective synthesis of d-galacto-isofagomine
journal, May 2010
- Spanu, Pietro; Candia, Cristina de; Ulgheri, Fausta
- Tetrahedron Letters, Vol. 51, Issue 18
Iminosugars past, present and future: medicines for tomorrow
journal, February 2011
- Horne, Graeme; Wilson, Francis X.; Tinsley, Jon
- Drug Discovery Today, Vol. 16, Issue 3-4
Promising results of the chaperone effect caused by iminosugars and aminocyclitol derivatives on mutant glucocerebrosidases causing Gaucher disease
journal, March 2009
- Sánchez-Ollé, Gessamí; Duque, Joana; Egido-Gabás, Meritxell
- Blood Cells, Molecules, and Diseases, Vol. 42, Issue 2
electronic Ligand Builder and Optimization Workbench ( eLBOW ): a tool for ligand coordinate and restraint generation
journal, September 2009
- Moriarty, Nigel W.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
- Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 10
Delivery of endocytosed membrane proteins to the lysosome
journal, April 2009
- Pryor, Paul R.; Luzio, J. Paul
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1793, Issue 4
A Chaperone Enhances Blood α-Glucosidase Activity in Pompe Disease Patients Treated With Enzyme Replacement Therapy
journal, November 2014
- Parenti, Giancarlo; Fecarotta, Simona; la Marca, Giancarlo
- Molecular Therapy, Vol. 22, Issue 11
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
journal, July 2007
- Brumshtein, Boris; Greenblatt, Harry M.; Butters, Terry D.
- Journal of Biological Chemistry, Vol. 282, Issue 39
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
journal, July 2000
- Asano, Naoki; Ishii, Satoshi; Kizu, Haruhisa
- European Journal of Biochemistry, Vol. 267, Issue 13
The Pharmacological Chaperone N-butyldeoxynojirimycin Enhances Enzyme Replacement Therapy in Pompe Disease Fibroblasts
journal, June 2009
- Porto, Caterina; Cardone, Monica; Fontana, Federica
- Molecular Therapy, Vol. 17, Issue 6
Isofagomine increases lysosomal delivery of exogenous glucocerebrosidase
journal, May 2008
- Shen, Jin-Song; Edwards, Nancy J.; Hong, Young Bin
- Biochemical and Biophysical Research Communications, Vol. 369, Issue 4
XDS
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
LigPlot+: Multiple Ligand–Protein Interaction Diagrams for Drug Discovery
journal, October 2011
- Laskowski, Roman A.; Swindells, Mark B.
- Journal of Chemical Information and Modeling, Vol. 51, Issue 10
Correlation between enzyme activity and substrate storage in a cell culture model system for Gaucher disease
journal, January 2004
- Schueler, U. H.; Kolter, T.; Kaneski, C. R.
- Journal of Inherited Metabolic Disease, Vol. 27, Issue 5
GALC Deletions Increase the Risk of Primary Open-Angle Glaucoma: The Role of Mendelian Variants in Complex Disease
journal, November 2011
- Liu, Yutao; Gibson, Jason; Wheeler, Joshua
- PLoS ONE, Vol. 6, Issue 11
Lysosomal Storage Diseases: From Pathophysiology to Therapy
journal, January 2015
- Parenti, Giancarlo; Andria, Generoso; Ballabio, Andrea
- Annual Review of Medicine, Vol. 66, Issue 1
An extremely potent inhibitor for β-galactosidase
journal, June 1995
- Ichikawa, Yoshitaka; Igarashi, Yasuhiro
- Tetrahedron Letters, Vol. 36, Issue 26
A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease
journal, January 1995
- Rafi, Mohammad A.; Luzi, Paola; Chen, Yue Qun
- Human Molecular Genetics, Vol. 4, Issue 8
Asymmetric Synthesis of All Stereoisomers of Isofagomine Using [2,3]-Wittig Rearrangement
journal, January 2007
- Takahata, Hiroki; Mihara, Yukiko; Ojima, Hidetomo
- HETEROCYCLES, Vol. 72, Issue 1
Enzyme Replacement for Lysosomal Diseases
journal, February 2006
- Brady, Roscoe O.
- Annual Review of Medicine, Vol. 57, Issue 1
Cellular effects of deoxynojirimycin analogues: uptake, retention and inhibition of glycosphingolipid biosynthesis
journal, July 2004
- Mellor, Howard R.; Neville, David C. A.; Harvey, David J.
- Biochemical Journal, Vol. 381, Issue 3
Targeting of the CNS in MPS-IH Using a Nonviral Transferrin-α-l-iduronidase Fusion Gene Product
journal, August 2008
- Osborn, Mark J.; McElmurry, Ron T.; Peacock, Brandon
- Molecular Therapy, Vol. 16, Issue 8
FEM: Feature Enhanced Map
journal, August 2014
- Afonine, Pavel
- Acta Crystallographica Section A Foundations and Advances, Vol. 70, Issue a1
The galactocerebrosidase enzyme contributes to the maintenance of a functional hematopoietic stem cell niche
journal, September 2010
- Visigalli, Ilaria; Ungari, Silvia; Martino, Sabata
- Blood, Vol. 116, Issue 11
Molecular heterogeneity of Krabbe disease
journal, April 1999
- Fu, L.; Inui, K.; Nishigaki, T.
- Journal of Inherited Metabolic Disease, Vol. 22, Issue 2, p. 155-162
Two different mutations are responsible for Krabbe disease in the Druze and Moslem Arab populations in Israel
journal, March 1996
- Rafi, Mohammad A.; Luzi, Paola; Zlotogora, Joel
- Human Genetics, Vol. 97, Issue 3
Immune Response to Enzyme Replacement Therapy in Lysosomal Storage Disorder Patients and Animal Models
journal, October 1999
- Brooks, Doug A.
- Molecular Genetics and Metabolism, Vol. 68, Issue 2
The Phenix software for automated determination of macromolecular structures
journal, September 2011
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Methods, Vol. 55, Issue 1
Krabbe's Disease: Globoid Cell Type of Leukodystrophy
journal, January 1963
- D'Agostino, Anthony N.
- Archives of Neurology, Vol. 8, Issue 1
xia2 : an expert system for macromolecular crystallography data reduction
journal, December 2009
- Winter, G.
- Journal of Applied Crystallography, Vol. 43, Issue 1
Microwave-assisted synthesis of pyrrolidine derivatives
journal, August 2009
- Chang, Yuan-Chun; Chir, Jiun-Ly; Tsai, Shuan-Yi
- Tetrahedron Letters, Vol. 50, Issue 34
Molecular genetics of Krabbe disease (globoid cell leukodystrophy): Diagnostic and clinical implications
journal, January 1997
- Wenger, David A.; Rafi, Mohammad A.; Luzi, Paola
- Human Mutation, Vol. 10, Issue 4
General atomic and molecular electronic structure system
journal, November 1993
- Schmidt, Michael W.; Baldridge, Kim K.; Boatz, Jerry A.
- Journal of Computational Chemistry, Vol. 14, Issue 11, p. 1347-1363
Dividing Cells Regulate Their Lipid Composition and Localization
journal, January 2014
- Atilla-Gokcumen, G. Ekin; Muro, Eleonora; Relat-Goberna, Josep
- Cell, Vol. 156, Issue 3
Using pharmacological chaperones to restore proteostasis
journal, May 2014
- Wang, Ya-Juan; Di, Xiao-Jing; Mu, Ting-Wei
- Pharmacological Research, Vol. 83
Nrf2, a multi-organ protector?
journal, July 2005
- Lee, Jong-Min; Li, Jiang; Johnson, Delinda A.
- The FASEB Journal, Vol. 19, Issue 9
Structures and mechanisms of glycosyl hydrolases
journal, September 1995
- Davies, Gideon; Henrissat, Bernard
- Structure, Vol. 3, Issue 9
MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009
- Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells: Galactocerebrosidase in Cancer Cells
journal, January 2005
- Beier, Ulf Henning; Görögh, Tibor
- International Journal of Cancer, Vol. 115, Issue 1
Structure of acid β-glucosidase with pharmacological chaperone provides insight into Gaucher disease
journal, December 2006
- Lieberman, Raquel L.; Wustman, Brandon A.; Huertas, Pedro
- Nature Chemical Biology, Vol. 3, Issue 2
Structural snapshots illustrate the catalytic cycle of -galactocerebrosidase, the defective enzyme in Krabbe disease
journal, December 2013
- Hill, C. H.; Graham, S. C.; Read, R. J.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 51
Features and development of Coot
journal, March 2010
- Emsley, P.; Lohkamp, B.; Scott, W. G.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
A New Route to Diverse 1-Azasugars from N -Boc-5-hydroxy-3-piperidene as a Common Building Block
journal, June 2005
- Ouchi, Hidekazu; Mihara, Yukiko; Takahata, Hiroki
- The Journal of Organic Chemistry, Vol. 70, Issue 13
A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo
journal, June 2008
- Yuzwa, Scott A.; Macauley, Matthew S.; Heinonen, Julia E.
- Nature Chemical Biology, Vol. 4, Issue 8
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
journal, June 1997
- Andersen, Sören M.; Ebner, Michael; Ekhart, Christian W.
- Carbohydrate Research, Vol. 301, Issue 3-4
Pathology and Current Treatment of Neurodegenerative Sphingolipidoses
journal, August 2010
- Eckhardt, Matthias
- NeuroMolecular Medicine, Vol. 12, Issue 4
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
1-Azafagomine: A Hydroxyhexahydropyridazine That Potently Inhibits Enzymatic Glycoside Cleavage
journal, June 1997
- Bols, Mikael; Hazell, Rita G.; Thomsen, Ib B.
- Chemistry - A European Journal, Vol. 3, Issue 6
Pharmacological chaperoning: A primer on mechanism and pharmacology
journal, May 2014
- Leidenheimer, Nancy J.; Ryder, Katelyn G.
- Pharmacological Research, Vol. 83
A single mutation in the GALC gene is responsible for the majority of late onset Krabbe disease patients in the Catania (Sicily, Italy) region
journal, January 2007
- Lissens, Willy; Arena, Alessia; Seneca, Sara
- Human Mutation, Vol. 28, Issue 7
Mannose-6-phosphate pathway: A review on its role in lysosomal function and dysfunction
journal, April 2012
- Coutinho, Maria Francisca; Prata, Maria João; Alves, Sandra
- Molecular Genetics and Metabolism, Vol. 105, Issue 4
Treating lysosomal storage diseases with pharmacological chaperones: from concept to clinics
journal, August 2009
- Parenti, Giancarlo
- EMBO Molecular Medicine, Vol. 1, Issue 5
Pharmacological chaperones increase residual β-galactocerebrosidase activity in fibroblasts from Krabbe patients
journal, August 2014
- Berardi, Anna Sara; Pannuzzo, Giovanna; Graziano, Adriana
- Molecular Genetics and Metabolism, Vol. 112, Issue 4
The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability
journal, September 2007
- Niesen, Frank H.; Berglund, Helena; Vedadi, Masoud
- Nature Protocols, Vol. 2, Issue 9
Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients
journal, August 1997
- Furuya, H.; Kukita, Yoh-ji; Nagano, Sukehisa
- Human Genetics, Vol. 100, Issue 3-4
Aza-Claisen rearrangement of 2-C-hydroxymethyl glycals as a versatile strategy towards synthesis of isofagomine and related biologically important azasugars
journal, January 2012
- Reddy, Y. Suman; Kancharla, Pavan K.; Roy, Rashmi
- Organic & Biomolecular Chemistry, Vol. 10, Issue 14
Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype–phenotype correlation
journal, April 2006
- Xu, Chengzhe; Sakai, Norio; Taniike, Masako
- Journal of Human Genetics, Vol. 51, Issue 6
Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease
journal, September 2010
- Tappino, Barbara; Biancheri, Roberta; Mort, Matthew
- Human Mutation, Vol. 31, Issue 12
Retroviral Vector-Mediated Transfer of the Galactocerebrosidase (GALC) cDNA Leads to Overexpression and Transfer of GALC Activity to Neighboring Cells
journal, August 1996
- Rafi, Mohammad A.; Fugaro, Joseph; Amini, Shohreh
- Biochemical and Molecular Medicine, Vol. 58, Issue 2
A Role for Protein Misfolding in Immunogenicity of Biopharmaceuticals
journal, November 2006
- Maas, Coen; Hermeling, Suzanne; Bouma, Barend
- Journal of Biological Chemistry, Vol. 282, Issue 4
E NZYME T HERAPY FOR L YSOSOMAL S TORAGE D ISEASE : Principles, Practice, and Prospects
journal, September 2003
- Grabowski, Gregory A.; Hopkin, Robert J.
- Annual Review of Genomics and Human Genetics, Vol. 4, Issue 1
Iminosugar-Based Galactoside Mimics as Inhibitors of Galactocerebrosidase: SAR Studies and Comparison with Other Lysosomal Galactosidases
journal, November 2014
- Biela-Banaś, Anna; Oulaïdi, Farah; Front, Sophie
- ChemMedChem, Vol. 9, Issue 12
Works referencing / citing this record:
X-Ray Crystallography in Structure-Function Characterization of Therapeutic Enzymes
book, September 2019
- Papageorgiou, Anastassios C.
- Advances in Experimental Medicine and Biology
Synthesis and evaluation of galacto-noeurostegine and its 2-deoxy analogue as glycosidase inhibitors
journal, January 2015
- Salamone, Stéphane; Clement, Lise L.; Viuff, Agnete H.
- Organic & Biomolecular Chemistry, Vol. 13, Issue 29
Pharmaceutical Chaperones and Proteostasis Regulators in the Therapy of Lysosomal Storage Disorders: Current Perspective and Future Promises
journal, July 2017
- Mohamed, Fedah E.; Al-Gazali, Lihadh; Al-Jasmi, Fatma
- Frontiers in Pharmacology, Vol. 8
Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses
journal, December 2019
- Losada Díaz, Juan Camilo; Cepeda del Castillo, Jacobo; Rodriguez-López, Edwin Alexander
- International Journal of Molecular Sciences, Vol. 21, Issue 1