Developing inhibitors of glycan processing enzymes as tools for enabling glycobiology

Nature Chemical Biology

Volumn 8, Issue 8, 2012, Pages 683-694

  Gloster, Tracey M ^a,b   Vocadlo, David J ^a,b  

^a SIMON FRASER UNIVERSITY   (Canada)

^b UNIVERSITY OF ST ANDREWS   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 DEOXYNOJIRIMYCIN; ACARBOSE; ALPHA GLUCOSIDASE; ALPHA GLUCOSIDASE INHIBITOR; AMYLASE; AMYLASE INHIBITOR; BETA GALACTOSIDASE; CARBOHYDRATE DERIVATIVE; GLUCOSE; GLUCOSYLCERAMIDASE; GLYCAN; GLYCOCONJUGATE; GLYCONOHYDROXIMOLACTAM; GLYCOSIDASE; GLYCOSIDASE INHIBITOR; GLYCOSYLTRANSFERASE; ISOFAGOMINE; KOTALANOL; MIGALASTAT; MIGLITOL; N NONYL DEOPXYNOJIRIMYCIN; NATURAL PRODUCT; NOJIRIMYCIN; OLIGOSACCHARIDE; PLANT EXTRACT; SALACIA RETICULATA EXTRACT; SALACINOL; THIAZOLE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VOGLIBOSE;

CELL ADHESION; CELL DIFFERENTIATION; CHEMICAL STRUCTURE; DRUG BINDING SITE; DRUG DESIGN; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; DRUG TARGETING; ENZYME ACTIVE SITE; ENZYME INHIBITION; ENZYME MECHANISM; FABRY DISEASE; GAUCHER DISEASE; GLUCOSE HOMEOSTASIS; GLYCOBIOLOGY; GLYCOGEN STORAGE DISEASE TYPE 2; HIGH THROUGHPUT SCREENING; HYDROPHOBICITY; INFLAMMATION; LIPOPHILICITY; MAMMAL; METABOLISM; NONHUMAN; PRIORITY JOURNAL; PROTEIN FAMILY; QUALITY CONTROL; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; TISSUE SPECIFICITY;

MAMMALIA;

EID: 84864254567     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/nchembio.1029     Document Type: Review

References (100)

1. Feizi, T. Demonstration by monoclonal antibodies that carbohydrate structures of glycoproteins and glycolipids are onco-developmental antigens. Nature 314, 53-57 (1985).
2. Partridge, E.A. et al. Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis. Science 306, 120-124 (2004).
3. Da Silva, J.S., Hasegawa, T., Miyagi, T., Dotti, C.G. & Abad-Rodriguez, J. Asymmetric membrane ganglioside sialidase activity specifies axonal fate. Nat. Neurosci. 8, 606-615 (2005).
4. Sackstein, R. et al. Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nat. Med. 14, 181-187 (2008).
5. Reichner, J.S., Helgemo, S.L. & Hart, G.W. Recycling cell surface glycoproteins undergo limited oligosaccharide reprocessing in LEC1 mutant Chinese hamster ovary cells. Glycobiology 8, 1173-1182 (1998).
6. Määttänen, P., Gehring, K., Bergeron, J.J. & Thomas, D.Y. Protein quality control in the ER: The recognition of misfolded proteins. Semin. Cell Dev. Biol. 21, 500-511 (2010).
7. Kornfeld, S. Trafficking of lysosomal enzymes. FASEB J. 1, 462-468 (1987).
8. Moloney, D.J. et al. Fringe is a glycosyltransferase that modifies Notch. Nature 406, 369-375 (2000).
9. Phillips, M.L. et al. ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-LeX. Science 250, 1130-1132 (1990).
10. Ohtsubo, K. et al. Dietary and genetic control of glucose transporter 2 glycosylation promotes insulin secretion in suppressing diabetes. Cell 123, 1307-1321 (2005).
11. Frye, S.V. The art of the chemical probe. Nat. Chem. Biol. 6, 159-161 (2010).
12. Abad-Zapatero, C. Ligand efficiency indices for effective drug discovery. Expert Opin. Drug Discov. 2, 469-488 (2007).
13. Leeson, P.D. & Springthorpe, B. The influence of drug-like concepts on decisionmaking in medicinal chemistry. Nat. Rev. Drug Discov. 6, 881-890 (2007).
14. Cantarel, B.L. et al. The Carbohydrate-Active EnZymes database (CAZy): An expert resource for glycogenomics. Nucleic Acids Res. 37, D233-D238 (2009).
15. Vocadlo, D.J. & Davies, G.J. Mechanistic insights into glycosidase chemistry. Curr. Opin. Chem. Biol. 12, 539-555 (2008).
16. Mader, M.M. & Bartlett, P.A. Binding energy and catalysis: The implications for transition-state analogs and catalytic antibodies. Chem. Rev. 97, 1281-1302 (1997).
17. Gloster, T.M. & Davies, G.J. Glycosidase inhibition: Assessing mimicry of the transition state. Org. Biomol. Chem. 8, 305-320 (2010).
18. Gloster, T.M. et al. Glycosidase inhibition: An assessment of the binding of eighteen putative transition-state mimics. J. Am. Chem. Soc. 129, 2345-2354 (2007).
19. Tropak, M.B., Blanchard, J.E., Withers, S.G., Brown, E.D. & Mahuran, D. High-throughput screening for human lysosomal β-N-acetyl hexosaminidase inhibitors acting as pharmacological chaperones. Chem. Biol. 14, 153-164 (2007).
20. Cole, D.C. et al. Identification and characterization of acidic mammalian chitinase inhibitors. J. Med. Chem. 53, 6122-6128 (2010).
21. Zheng, W. et al. Three classes of glucocerebrosidase inhibitors identified by quantitative high-throughput screening are chaperone leads for Gaucher disease. Proc. Natl. Acad. Sci. USA 104, 13192-13197 (2007).
22. Nahoum, V. et al. Crystal structures of human pancreatic α-amylase in complex with carbohydrate and proteinaceous inhibitors. Biochem. J. 346, 201-208 (2000).
23. Qin, X. et al. Structures of human pancreatic a-amylase in complex with acarviostatins: Implications for drug design against type II diabetes. J. Struct. Biol. 174, 196-202 (2011).
24. Tarling, C.A. et al. The search for novel human pancreatic a-amylase inhibitors: High-throughput screening of terrestrial and marine natural product extracts. ChemBioChem 9, 433-438 (2008).
25. Kageyama, S., Nakamichi, N., Sekino, H. & Nakano, S. Comparison of the effects of acarbose and voglibose in healthy subjects. Clin. Ther. 19, 720-729 (1997).
26. Madar, Z. The effect of acarbose and miglitol (BAY-M-1099) on postprandial glucose levels following ingestion of various sources of starch by nondiabetic and streptozotocin-induced diabetic rats. J. Nutr. 119, 2023-2029 (1989).
27. Sim, L. et al. Structural basis for substrate selectivity in human maltaseglucoamylase and sucrase-isomaltase N-terminal domains. J. Biol. Chem. 285, 17763-17770 (2010).
28. Benalla, W., Bellahcen, S. & Bnouham, M. Antidiabetic medicinal plants as a source of alpha glucosidase inhibitors. Curr. Diabetes Rev. 6, 247-254 (2010).
29. Parenti, G. Treating lysosomal storage diseases with pharmacological chaperones: From concept to clinics. EMBO Mol. Med. 1, 268-279 (2009).
30. Sawkar, A.R. et al. Chemical chaperones increase the cellular activity of N370S β-glucosidase: A therapeutic strategy for Gaucher disease. Proc. Natl. Acad. Sci. USA 99, 15428-15433 (2002).
31. Steet, R.A. et al. The iminosugar isofagomine increases the activity of N370S mutant acid beta-glucosidase in Gaucher fibroblasts by several mechanisms. Proc. Natl. Acad. Sci. USA 103, 13813-13818 (2006).
32. Khanna, R. et al. The pharmacological chaperone isofagomine increases the activity of the Gaucher disease L444P mutant form of β-glucosidase. FEBS J. 277, 1618-1638 (2010).
33. Khanna, R. et al. The pharmacological chaperone 1-deoxygalactonojirimycin reduces tissue globotriaosylceramide levels in a mouse model of Fabry disease. Mol. Ther. 18, 23-33 (2010).
34. Clarke, J.T. et al. An open-label Phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay-Sachs or Sandhoff variants). Mol. Genet. Metab. 102, 6-12 (2011).
35. Shen, J.S., Edwards, N.J., Hong, Y.B. & Murray, G.J. Isofagomine increases lysosomal delivery of exogenous glucocerebrosidase. Biochem. Biophys. Res. Commun. 369, 1071-1075 (2008).
36. Hart, G.W., Housley, M.P. & Slawson, C. Cycling of O-linked b-Nacetylglucosamine on nucleocytoplasmic proteins. Nature 446, 1017-1022 (2007).
37. Laczy, B., Marsh, S.A., Brocks, C.A., Wittmann, I. & Chatham, J.C. Inhibition of O-GlcNAcase in perfused rat hearts by NAG-thiazolines at the time of reperfusion is cardioprotective in an O-GlcNAc-dependent manner. Am. J. Physiol. Heart Circ. Physiol. 299, H1715-H1727 (2010).
38. Caldwell, S.A. et al. Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1. Oncogene 29, 2831-2842 (2010).
39. Shi, Y. et al. Aberrant O-GlcNAcylation characterizes chronic lymphocytic leukemia. Leukemia 24, 1588-1598 (2010).
40. Liu, F., Iqbal, K., Grundke-Iqbal, I., Hart, G.W. & Gong, C.X. O-GlcNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer's disease. Proc. Natl. Acad. Sci. USA 101, 10804-10809 (2004).
41. Yuzwa, S.A. et al. A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nat. Chem. Biol. 4, 483-490 (2008).
42. Lefebvre, T. et al. Evidence of a balance between phosphorylation and O-GlcNAc glycosylation of Tau proteins-a role in nuclear localization. Biochim. Biophys. Acta 1619, 167-176 (2003).
43. Macauley, M.S., Whitworth, G.E., Debowski, A.W., Chin, D. & Vocadlo, D.J. O-GlcNAcase uses substrate-assisted catalysis. J. Biol. Chem. 280, 25313-25322 (2005).
44. Whitworth, G.E. et al. Analysis of PUGNAc and NAG-thiazoline as transition state analogues for human O-GlcNAcase: Mechanistic and structural insights into inhibitor selectivity and transition state poise. J. Am. Chem. Soc. 129, 635-644 (2007).
45. Macauley, M.S., Shan, X., Yuzwa, S.A., Gloster, T.M. & Vocadlo, D.J. Elevation of Global O-GlcNAc in rodents using a selective O-GlcNAcase inhibitor does not cause insulin resistance or perturb glucohomeostasis. Chem. Biol. 17, 949-958 (2010).
46. Dennis, R.J. et al. Structure and mechanism of a bacterial β-glucosaminidase having O-GlcNAcase activity. Nat. Struct. Mol. Biol. 13, 365-371 (2006).
47. Dorfmueller, H.C., Borodkin, V.S., Schimpl, M. & Van Aalten, D.M. GlcNAcstatins are nanomolar inhibitors of human O-GlcNAcase inducing cellular hyper-O-GlcNAcylation. Biochem. J. 420, 221-227 (2009).
48. Dorfmueller, H.C. et al. GlcNAcstatin: A picomolar, selective O-GlcNAcase inhibitor that modulates intracellular O-glcNAcylation levels. J. Am. Chem. Soc. 128, 16484-16485 (2006).
49. Dorfmueller, H.C. et al. Cell-penetrant, nanomolar O-GlcNAcase inhibitors selective against lysosomal hexosaminidases. Chem. Biol. 17, 1250-1255 (2010).
50. Dorfmueller, H.C. & Van Aalten, D.M. Screening-based discovery of drug-like O-GlcNAcase inhibitor scaffolds. FEBS Lett. 584, 694-700 (2010).
51. Yuzwa, S.A. et al. Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation. Nat. Chem. Biol. 8, 393-399 (2012).
52. Zhu, Z. et al. Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation. Science 304, 1678-1682 (2004).
53. Sutherland, T.E., Maizels, R.M. & Allen, J.E. Chitinases and chitinase-like proteins: Potential therapeutic targets for the treatment of T-helper type 2 allergies. Clin. Exp. Allergy 39, 943-955 (2009).
54. Olland, A.M. et al. Triad of polar residues implicated in pH specificity of acidic mammalian chitinase. Protein Sci. 18, 569-578 (2009).
55. Andersen, O.A., Nathubhai, A., Dixon, M.J., Eggleston, I.M. & Van Aalten, D.M. Structure-based dissection of the natural product cyclopentapeptide chitinase inhibitor argifin. Chem. Biol. 15, 295-301 (2008).
56. Fitz, L.J. et al. Acidic mammalian chitinase is not a critical target for allergic airway disease. Am. J. Respir. Cell Mol. Biol. 46, 71-79 (2012).
57. Lairson, L.L., Henrissat, B., Davies, G.J. & Withers, S.G. Glycosyltransferases: Tructures, functions, and mechanisms. Annu. Rev. Biochem. 77, 521-555 (2008).
58. Soya, N., Fang, Y., Palcic, M.M. & Klassen, J.S. Trapping and characterization of covalent intermediates of mutant retaining glycosyltransferases. Glycobiology 21, 547-552 (2011).
59. Lee, S.S. et al. Mechanistic evidence for a front-side, SNi-type reaction in a retaining glycosyltransferase. Nat. Chem. Biol. 7, 631-638 (2011).
60. Müller, B., Schaub, C. & Schmidt, R. Efficient sialyltransferase inhibitors based on transition-state analogues of the sialyl donor. Angew. Chem. Int. Ed. Engl. 37, 2893-2897 (1998).
61. Lee, L.V. et al. A potent and highly selective inhibitor of human α-1,3-fucosyltransferase via click chemistry. J. Am. Chem. Soc. 125, 9588-9589 (2003).
62. Hosoguchi, K. et al. An efficient approach to the discovery of potent inhibitors against glycosyltransferases. J. Med. Chem. 53, 5607-5619 (2010).
63. Rillahan, C.D., Brown, S.J., Register, A.C., Rosen, H. & Paulson, J.C. Highthroughput screening for inhibitors of sialyl- and fucosyltransferases. Angew. Chem. Int. Edn. Engl. 50, 12534-12537 (2011).
64. Fuster, M.M. & Esko, J.D. The sweet and sour of cancer: Glycans as novel therapeutic targets. Nat. Rev. Cancer 5, 526-542 (2005).
65. Lowe, J.B. & Marth, J.D. A genetic approach to mammalian glycan function. Annu. Rev. Biochem. 72, 643-691 (2003).
66. Pesnot, T., Jorgensen, R., Palcic, M.M. & Wagner, G.K. Structural and mechanistic basis for a new mode of glycosyltransferase inhibition. Nat. Chem. Biol. 6, 321-323 (2010).
67. Wang, R. et al. A search for pyrophosphate mimics for the development of substrates and inhibitors of glycosyltransferases. Bioorg. Med. Chem. 5, 661-672 (1997).
68. Niewiadomski, S. et al. Rationally designed squaryldiamides-a novel class of sugar-nucleotide mimics? Org. Biomol. Chem. 8, 3488-3499 (2010).
69. Mahoney, W.C. & Duksin, D. Biological activities of the two major components of tunicamycin. J. Biol. Chem. 254, 6572-6576 (1979).
70. Platt, F.M., Neises, G.R., Dwek, R.A. & Butters, T.D. N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis. J. Biol. Chem. 269, 8362-8365 (1994).
71. Vunnam, R.R. & Radin, N.S. Analogs of ceramide that inhibit glucocerebroside synthetase in mouse brain. Chem. Phys. Lipids 26, 265-278 (1980).
72. Lukina, E. et al. A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood 116, 893-899 (2010).
73. Masciullo, M. et al. Substrate reduction therapy with miglustat in chronic GM2 gangliosidosis type Sandhoff: Results of a 3-year follow-up. J. Inherit. Metab. Dis. published online, doi:10.1007/s10545-010-9186-3 (7 September 2010).
74. Patterson, M.C. et al. Long-term miglustat therapy in children with Niemann-Pick disease type C. J. Child Neurol. 25, 300-305 (2010).
75. Zhao, H. et al. Inhibiting glycosphingolipid synthesis improves glycemic control and insulin sensitivity in animal models of type 2 diabetes. Diabetes 56, 1210-1218 (2007).
76. Natoli, T.A. et al. Inhibition of glucosylceramide accumulation results in effective blockade of polycystic kidney disease in mouse models. Nat. Med. 16, 788-792 (2010).
77. Kuan, S.F., Byrd, J.C., Basbaum, C. & Kim, Y.S. Inhibition of mucin glycosylation by aryl-N-acetyl-α-galactosaminides in human colon cancer cells. J. Biol. Chem. 264, 19271-19277 (1989).
78. Brown, J.R. et al. A disaccharide-based inhibitor of glycosylation attenuates metastatic tumor cell dissemination. Clin. Cancer Res. 12, 2894-2901 (2006).
79. Laferté, S., Chan, N.W., Sujino, K., Lowary, T.L. & Palcic, M.M. Intracellular inhibition of blood group A glycosyltransferase. Eur. J. Biochem. 267, 4840-4849 (2000).
80. Brown, J.R. et al. Deoxygenated disaccharide analogs as specific inhibitors of β1-4-galactosyltransferase 1 and selectin-mediated tumor metastasis. J. Biol. Chem. 284, 4952-4959 (2009).
81. Ralton, J.E., Milne, K.G., Guther, M.L., Field, R.A. & Ferguson, M.A. The mechanism of inhibition of glycosylphosphatidylinositol anchor biosynthesis in Trypanosoma brucei by mannosamine. J. Biol. Chem. 268, 24183-24189 (1993).
82. Dimitroff, C.J., Kupper, T.S. & Sackstein, R. Prevention of leukocyte migration to inflamed skin with a novel fluorosugar modifier of cutaneous lymphocyte-associated antigen. J. Clin. Invest. 112, 1008-1018 (2003).
83. Barthel, S.R. et al. Peracetylated 4-fluoro-glucosamine reduces the content and repertoire of N- and O-glycans without direct incorporation. J. Biol. Chem. 286, 21717-21731 (2011).
84. Gloster, T.M. et al. Hijacking a biosynthetic pathway yields a glycosyltransferase inhibitor within cells. Nat. Chem. Biol. 7, 174-181 (2011).
85. Rillahan, C.D. et al. Global metabolic inhibitors of sialyl- and fucosyltransferases remodel the glycome. Nat. Chem. Biol. 8, 661-668 (2012).
86. Gross, B.J., Swoboda, J.G. & Walker, S. A strategy to discover inhibitors of O-linked glycosylation. J. Am. Chem. Soc. 130, 440-441 (2008).
87. Dehennaut, V. et al. O-linked N-acetylglucosaminyltransferase inhibition prevents G2/M transition in Xenopus laevis oocytes. J. Biol. Chem. 282, 12527-12536 (2007).
88. Lazarus, M.B., Nam, Y., Jiang, J., Sliz, P. & Walker, S. Structure of human O-GlcNAc transferase and its complex with a peptide substrate. Nature 469, 564-567 (2011).
89. Lee, K.Y. et al. The hexapeptide inhibitor of Galα1,3GalNAc- specific α2,3-sialyltransferase as a generic inhibitor of sialyltransferases. J. Biol. Chem. 277, 49341-49351 (2002).
90. Chiang, C.H. et al. A novel sialyltransferase inhibitor AL10 suppresses invasion and metastasis of lung cancer cells by inhibiting integrin-mediated signaling. J. Cell. Physiol. 223, 492-499 (2010).
91. Chen, J.Y. et al. A novel sialyltransferase inhibitor suppresses FAK/paxillin signaling and cancer angiogenesis and metastasis pathways. Cancer Res. 71, 473-483 (2011).
92. Yamashita, T. et al. A vital role for glycosphingolipid synthesis during development and differentiation. Proc. Natl. Acad. Sci. USA 96, 9142-9147 (1999).
93. Platt, F.M. et al. Prevention of lysosomal storage in Tay-Sachs mice treated with N-butyldeoxynojirimycin. Science 276, 428-431 (1997).
94. Cox, T. et al. Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet 355, 1481-1485 (2000).
95. Rishton, G.M. Nonleadlikeness and leadlikeness in biochemical screening. Drug Discov. Today 8, 86-96 (2003).
96. Shah, N., Kuntz, D.A. & Rose, D.R. Golgi α-mannosidase II cleaves two sugars sequentially in the same catalytic site. Proc. Natl. Acad. Sci. USA 105, 9570-9575 (2008).
97. Lillelund, V.H., Jensen, H.H., Liang, X. & Bols, M. Recent developments of transition-state analogue glycosidase inhibitors of non-natural product origin. Chem. Rev. 102, 515-553 (2002).
98. von Itzstein, M. The war against influenza: Discovery and development of sialidase inhibitors. Nat. Rev. Drug Discov. 6, 967-974 (2007).
99. Ho, C.W. et al. Development of GlcNAc-inspired iminocyclitiols as potent and selective N-acetyl-β-hexosaminidase inhibitors. ACS Chem. Biol. 5, 489-497 (2010).
100. Hrmova, M. et al. Structural rationale for low-nanomolar binding of transition state mimics to a family GH3 β-D-glucan glucohydrolase from barley. Biochemistry 44, 16529-16539 (2005).