中文
Earlier issues
Announcement
More
Progress in Chemistry 2014, Vol. 26 Issue (05): 889-897 DOI: 10.7536/PC131020 Previous Articles   Next Articles

• Review •

Small Molecular Pharmacological Chaperone for Gaucher Disease

Li Jing, Xie Xiaoli, Wang Jiajia, Wang Xiaomin, Li Jing*, Wang Peng*   

  1. College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology, Synergetic Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China
  • Received: Revised: Online: Published:
  • Supported by:

    The work was supported by the National Natural Science Foundation of China(No. 91013013, 31000371)

PDF ( 1663 ) Cited
Export

EndNote

Ris

BibTeX

Gaucher disease (GD) is a human autosomal recessive disorder mainly due to mutations in the gene encoding for the lysosomal enzyme acid β-glucocerebrosidase (GCase). It is the most common lysosomal storage disorder. Endoplasmic reticulum associated degradation (ERAD) and limitation for translocation to lysosome are two main pathological factors for GD. So far, enzyme replcement therapy (ERT) and substrate reduction therapy (SRT) are approved medical treatments for type Ⅰ GD patients with non-neurological involvement. However, they are intrinsically associated with low stability in biological media as well as the impossibility to cross the blood brain barrier (BBB). GCase competitive inhibitors can bind mutant GCase in cytoplasm with low concentration substrates, induce it fold and translocate it to lysosome. In lysosome with high concentration substrates, competitive inhibitors dissociate from GCase and release it. Therefore, PCs (pharmacological chaperones) based on competitive inhibitors become the most promising drugs. According to the research on GCase PC in our group, the structure and the catalytic mechanism of GCase and related GCase PCs are introduced. Particularly, the structure and activity relationships of deoxynojirimycin, 1,5-dideoxy-1,5-imino-D-xylitol, isofagomine, aminoinositol and bicyclic iminosugar are discussed emphatically. In addition, other non-sugar derived PCs are briefly introduced. Finally, we analysize the future prospect of GCase PCs and propose the directions in development.

Contents
1 Introduction
2 Structure and catalytic mechanism of GCase
3 GCase pharmacological chaperones
3.1 Deoxynojirimycin
3.2 1,5-dideoxy-1,5-imino-D -xylitol
3.3 Isofagomine
3.4 Aminoinositol
3.5 Bicyclic iminosugar
3.6 Other non-sugar derived pharmacological chaperones
4 Conclusion and outlook

Key words: gaucher disease, acid β-glucocerebrosidase, pharmacological chaperone

CLC Number: 

[1] Marco S, Michela P, Alberto R. Science, 2009, 325: 473.
[2] 江静雯(Jiang J W), 李晶(Li J), 刘文军(Liu W J). 生物工程学报(Chinese Journal of Biotechnology), 2011, 27(5): 724.
[3] 侯精飞(Hou J F), 叶新山(Ye X S). 中国科学:化学(Scientia Sinica Chimica), 2012, 42(12): 1732.
[4] Valverde A M, Reed S D, Schulman K A. Health Aff., 2012, 31(11): 2528.
[5] Aymami J, Barril X, Rodríguez-Pascau L, Martinell M. Pharm. Pat. Analyst., 2013, 1: 109.
[6] Hruska K S, LaMarca M E, Scott C R, Sidransky E. Hum. Mutat., 2008, 29: 567.
[7] Bendikov-Bar I, Horowitz M. Hum. Mutat., 2012, 33: 1398.
[8] Beutler E, Grabowsli G A. Gaucher disease. in The Metabolic and Molecular Based of Inherited Diseases. 8th ed. NY: McGraw-Hill, 2001. 3635.
[9] Suzuki Y, Ogawa S, Sakakibara Y. Perspect. Medicin. Chem., 2009, 3: 7.
[10] Hartl F U, Bracher A, Hayer-Hartl M. Nature, 2011, 475: 324.
[11] Boyd R E, Lee G, Rybczynski P, Benjamin E R, Khanna R, Wustman B A, Valencano K. J. Med. Chem., 2013, 56: 2705.
[12] Benito J M, García Fernández J M, Ortiz Mellet C. Expert. Opin. Ther. Pat., 2011, 6: 885.
[13] Dvir H, Harel M, McCarthy A A, Toker L, Silman I, Futerman A H, Sussman J. EMBO Reports, 2003, 7: 704.
[14] Brumshtein B, Greenblatt H M, Butters T D, Shaaltiel Y, Aviezer D, Silman I, Futerman A H, Sussman J L. J. Biol. Chem., 2007, 39: 29052.
[15] Sawkar A R, Cheng W C, Beutler E, Wong C H, Balch W E, Kelly J W. Proc. Natl. Acad. Sci. U. S. A., 2002, 24: 15428.
[16] Sawkar A R, Adamski-Werner S L, Cheng W C, Wong C H, Beutler E, Zimmer K P, Kelly J W. Chem. Biol., 2006, 4: 235.
[17] Trapero A, Llebaria A. Future. Med. Chem., 2013, 5(5): 573.
[18] Sawkar A R, Adamski-Werner S L, Cheng W C, Wong C H, Beutler E, Zimmer K P, Kelly J W. Chem. Biol., 2005, 12: 1235.
[19] Mellor H R, Platt F M, Dwek R A, Butters T D. Biochem. J., 2003, 374: 307.
[20] Frohlich R E G, Furneaux R H, Mahuran D J, Rigat B A, Stuzu A E, Tropak M B, Wicki J, Withers S G, Wrodnigg T M. Carbohydr. Res., 2010, 345: 1371.
[21] Doit J D, Moreno I G, Twigg G, Ortiz M C, Haupt K, Butters T D, Kovensky J, Gouin S G. J. Org. Chem., 2011, 76: 7757.
[22] Cheng W C, Weng C Y, Yun W Y, Chang S Y, Lin Y C, Tasi F J, Huang F Y, Chen Y R. Bioorg. Med. Chem., 2013, 21: 5021.
[23] Yu L, Ikeda K, Kato A, Adachi I, Godin G, Compain P, Martin O, Asano N. Bioorg. Med. Chem., 2006, 14: 7736.
[24] Wang G N, Reinkensmeier G, Zhang S W, Zhou J, Zhang L R, Zhang L H, Butters D, Ye S. J. Med. Chem., 2009, 52: 3146.
[25] Wang G N Twigg G, Butters T D, Zhang S, Zhang L, Zhang L H, Ye X S. Org. Biomol. Chem., 2012, 10: 2923.
[26] Compain P, Martin O R, Boucheron C, Godin G, Yu L, Ikeda K, Asano N. ChemBioChem., 2006, 7: 1356.
[27] Goddard-Borger E D, Tropak M B, Yonekawa S, Tysoe C, Mahuran D J, Withers S G. J. Med. Chem., 2012, 55: 2737.
[28] Chang H H, Asano N, Ishii S, Ichikawa Y, Fan J Q. FEBS. J., 2006, 273: 4082.
[29] Khanna R, Benjamin E R, Pellegrino L, Schilling A, Rigat B A, Soska R, Nafar H, Ranes B E, Feng J, Lun Y, Powe A C, Palling D J, Wustman B A, Schiffmann R, Mahuran D J, Lockhart D J, Valenzano K J. FEBS. J., 2010, 277: 1618.
[30] Steet R A, Chung S, Wustman B, Powe A, Do H, Kornfeld S A. Proc. Natl. Acad. Sci. U. S. A., 2006, 37: 13813.
[31] Steet R, Chung S, Lee W S, Pine C W, Do H, Kornfeld S. Biochem. Pharmacol., 2007, 73: 1376.
[32] Lieberman R L, Wustman B A, Huertas P, Powe A C Jr, Pine C W, Khanna R, Schlossmacher M G, Ringe D, Petsko G A. Nat. Chem. Biol., 2006, 3(2): 101.
[33] Amicus Therapeutics.[2011-2-11] http://www.amicustherapeutics. com/clinicaltrials
[34] Zhu X, Sheth K A, Li S, Chang H H, Fan J Q. Angew. Chem. Int. Ed., 2005, 44(45): 7450.
[35] Amicus T. WO 2005046612, 2005
[36] Ogawa S, Ashiura M, Uchida C, Watanabe S, Yamazaki C, Yamagishi K, Inokuchi J I. Bio. Med. Chem. Lett., 199, 6(8): 929.
[37] Yu Z, Sawkar A R, Whalen L J, Wong C H, Kelly J W. J. Med. Chem., 2007, 50: 94.
[38] Lei K, Ninomiya H, Suzuki M, Inoue T, Sawa M, Iida M, Ida H, Eto Y, Ogawa S, Ohno K, Suzuki Y. Biochim. Biophys. Acta, 2007, 1772: 587.
[39] Luan Z, Ninomiya H, Ohno K, Ogawa S, Kubo T, Iida M, Suzuki Y. Brain and Development, 2010, 32(10), 805.
[40] Trapero A, González-Bulnes P, Butters T D, Llebaria A J. Med. Chem., 2012, 55: 4479.
[41] Díaz L, Bujons J, Casas J, Llebaria A, Delgado A. J. Med. Chem., 2010, 53: 5248.
[42] Díaz L, Casas J, Bujons J, Llebaria A, Delgado A. J. Med. Chem., 2011, 54: 2069.
[43] Díaz P, Garcia M, Ortiz M, Fuentes J, Díaz A, Javier C, Garcia F. J. Org. Chem., 2000, 65: 136.
[44] Trapero A, Llebaria A. Med. Chem. Lett., 2011, 2: 614.
[45] Trapero A, Alfonso I, Butters TD, Llebaria A. J. Am. Chem. Soc., 2011, 133: 5474.
[46] Castilla J, Rísquez R, Cruz D, Higaki K, Nanba E, Ohno K, Suzuki Y, Díaz Y, Ortiz Mellet C, García Fernández J M, Castillón S. J. Med. Chem., 2012, 55: 6857.
[47] Li Z, Li T, Dai S, Xie X, Ma X, Zhao W, Zhang W, Li J, Wang P G. ChemBioChem., 2013, 14(10):1239.
[48] Maegawa G H, Tropak M B, Buttner J D, Rigat B A, Fuller M, Pandit D, Tang L, Kornhaber G J, Hamuro Y, Clarke J T, Mahuran D J. J. Bio. Chem., 2009, 284: 23502.
[49] Mahuran D J, Tropak M B, Buttner J D. WO 2009049421, 2009.
[50] Tropak M B, Kornhaber G J, Rigat B A, Maegawa G H, Buttner J D, Blanchard J E, Murphy C, Tuske S J, Coales S J, HamuroY, Brown E D, Mahuran D J. ChemBioChem., 2008, 9: 2650.
[51] Zheng W, Padia J, Urban D J, Jadhav A, Goker-Alpan O, Simeonov A, Goldin E, Auld D, Lamarca M E, Inglese J, Austin C P, Sidransky E. Proc. Natl. Acad. Sci. U. S. A., 2007, 104, 13192.
[52] Marugan J J, Zheng W, Motabar O, Southall N, Goldin E, Westbroek W, Stubblefield B K, Sidransky E, Aungst R A, Lea W A, Simeonov A, Leister W, Austin C P. J. Med. Chem., 2011, 54: 1033.
[53] Patnaik S, Zheng W, Choi J H, Motabar O, Southall N, Westbroek W, Lea W A, Velayati A, Goldin E, Sidransky E, Leister W, Marugan J J. J. Med. Chem., 2012, 55(12): 5734.
[1] Lili Cheng, Yun Zhang, Yekun Zhu, Ying Wu. Research and Prospect of Selective Oxidation of HMF [J]. Progress in Chemistry, 0, (): 8-0.
[2] Sun Pengfei, Hou Huanzhi, Fan Quli, Huang Wei. Synthesis and Application of Water-Soluble Conjugated Glycopolymer [J]. Progress in Chemistry, 2016, 28(10): 1489-1500.
[3] Wang Kerang. Chiral Supramolecular Assemblies Based on Aromatic Molecules-Carbohydrate Conjugates and Their Applications [J]. Progress in Chemistry, 2015, 27(6): 775-784.
[4] Wang Yihan, Wakisaka Minato. Nanofiber Fabrication Techniques and Its Applicability to Chitosan [J]. Progress in Chemistry, 2014, 26(11): 1821-1831.
[5] Shi Yugang, Dang Yali, Liu Yuhua, Bai Xue. Microbial and Chemical Production of Chondroitin Sulfate [J]. Progress in Chemistry, 2014, 26(08): 1378-1394.
[6] Xiong Yuting, Li Minmin, Xiong Peng, Yang Meng, Qing Guangyan, Sun Taolei. Artificial Carbohydrate Receptors in Aqueous Media [J]. Progress in Chemistry, 2014, 26(01): 48-60.
[7] Guo Xiao, Yan Yani, Zhang Yahong, Tang Yi. Heterogeneously Catalytic Transformation of Biomass-Derived Sugars [J]. Progress in Chemistry, 2013, 25(11): 1915-1927.
[8] Cao Linghua, He Yaowu, Li Gen, Haji Akber Aisa. Progress in Studies of Glycosylgunidines [J]. Progress in Chemistry, 2013, 25(08): 1334-1349.
[9] Li Tiehai, Guo Lina, Li Zhonghua, Wang Jiajia, Li Jing, Zhao Wei. O-GlcNAcase Inhibitors [J]. Progress in Chemistry, 2011, 23(8): 1657-1664.
[10] . Molecular Imprinting Technology Based on Cyclodextrins [J]. Progress in Chemistry, 2010, 22(05): 888-897.
[11] Ye Deju Wang Jinfang Zhang Dengyou Feng Enguang Jiang Hualiang Liu Hong. Advances in O-Sialylation [J]. Progress in Chemistry, 2010, 22(01): 91-100.
[12] Wang Hongmin Zhang Ping Huang Linjuan Wang Zhongfu. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry(MALDI) Application in Carbohydrates Analysis [J]. Progress in Chemistry, 2009, 21(6): 1335-1343.
[13] Zhu Wenbing Wu Fangying. Monosaccharide Recognition Based on Fluorescent Receptor Containing Boronic Acid [J]. Progress in Chemistry, 2009, 21(6): 1241-1253.
[14]

Wang Yadan, Wang Fei, Miao Zhiwei**, Chen Ruyu**

. Chiral Phosphorus Ligands Derived from Carbohydrate Scaffolds for Asymmetric Catalysis [J]. Progress in Chemistry, 2008, 20(12): 1923-1932.
[15] Huang Yi|Huang Jinhua|Xie Qingji**|Yao Shouzhuo**. Carbohydrate-Protein Interactions [J]. Progress in Chemistry, 2008, 20(06): 942-950.