全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
化学进展  2014 

戈谢病的药物分子伴侣

DOI: 10.7536/PC131020, PP. 889-897

Keywords: 戈谢病,β-葡萄糖脑苷脂酶,药物分子伴侣

Full-Text   Cite this paper   Add to My Lib

Abstract:

戈谢病(Gaucherdisease,GD)是一种由于β-酸性葡萄糖脑苷脂酶(acidβ-glucocerebrosidase,GCase)基因突变引起的常染色体隐性遗传疾病,也是发病率最高的溶酶体贮积病。突变GCase的内质网关联降解和靶向溶酶体运转受阻是主要病因。酶替代疗法(enzymereplacementtherapy,ERT)和底物降低疗法(substratereductiontherapy,SRT)是临床采用的主要治疗方法,但只对未涉及神经病变的Ⅰ型GD有效,且存在体内稳定性差和难以透过血脑屏障等弊端。GCase酶竞争性抑制剂可在低浓度底物的胞质中与突变酶结合,诱导酶折叠和运转;在高浓度底物的溶酶体中与酶解离,释放酶分子。因此,基于竞争性抑制剂的药物分子伴侣(pharmacologicalchaperone,PC)成为最具前景的药物。结合本课题组对GCasePC的研究,本文介绍了GCase的结构、催化机理及目前GCasePC的研究进展。重点讨论了脱氧野尻霉素类、环己亚胺醇类、C-糖苷衍生物、氨基环醇类和双环类PC的构效关系,简单介绍了其他非糖来源的PC,最后展望了GCasePC的前景,指出了今后研究中的发展方向。

References

[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]  Bendikov-Bar I, Horowitz M. Hum. Mutat., 2012, 33: 1398.
[4]  Boyd R E, Lee G, Rybczynski P, Benjamin E R, Khanna R, Wustman B A, Valencano K. J. Med. Chem., 2013, 56: 2705.
[5]  Benito J M, García Fernández J M, Ortiz Mellet C. Expert. Opin. Ther. Pat., 2011, 6: 885.
[6]  Dvir H, Harel M, McCarthy A A, Toker L, Silman I, Futerman A H, Sussman J. EMBO Reports, 2003, 7: 704.
[7]  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.
[8]  Trapero A, Llebaria A. Future. Med. Chem., 2013, 5(5): 573.
[9]  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.
[10]  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.
[11]  Chang H H, Asano N, Ishii S, Ichikawa Y, Fan J Q. FEBS. J., 2006, 273: 4082.
[12]  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.
[13]  Steet R A, Chung S, Wustman B, Powe A, Do H, Kornfeld S A. Proc. Natl. Acad. Sci. U. S. A., 2006, 37: 13813.
[14]  Steet R, Chung S, Lee W S, Pine C W, Do H, Kornfeld S. Biochem. Pharmacol., 2007, 73: 1376.
[15]  Amicus Therapeutics.[2011-2-11] http://www.amicustherapeutics. com/clinicaltrials
[16]  Zhu X, Sheth K A, Li S, Chang H H, Fan J Q. Angew. Chem. Int. Ed., 2005, 44(45): 7450.
[17]  Amicus T. WO 2005046612, 2005
[18]  Ogawa S, Ashiura M, Uchida C, Watanabe S, Yamazaki C, Yamagishi K, Inokuchi J I. Bio. Med. Chem. Lett., 199, 6(8): 929.
[19]  Yu Z, Sawkar A R, Whalen L J, Wong C H, Kelly J W. J. Med. Chem., 2007, 50: 94.
[20]  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.
[21]  Luan Z, Ninomiya H, Ohno K, Ogawa S, Kubo T, Iida M, Suzuki Y. Brain and Development, 2010, 32(10), 805.
[22]  Trapero A, González-Bulnes P, Butters T D, Llebaria A J. Med. Chem., 2012, 55: 4479.
[23]  Díaz L, Bujons J, Casas J, Llebaria A, Delgado A. J. Med. Chem., 2010, 53: 5248.
[24]  Díaz L, Casas J, Bujons J, Llebaria A, Delgado A. J. Med. Chem., 2011, 54: 2069.
[25]  Díaz P, Garcia M, Ortiz M, Fuentes J, Díaz A, Javier C, Garcia F. J. Org. Chem., 2000, 65: 136.
[26]  Trapero A, Llebaria A. Med. Chem. Lett., 2011, 2: 614.
[27]  Trapero A, Alfonso I, Butters TD, Llebaria A. J. Am. Chem. Soc., 2011, 133: 5474.
[28]  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.
[29]  Li Z, Li T, Dai S, Xie X, Ma X, Zhao W, Zhang W, Li J, Wang P G. ChemBioChem., 2013, 14(10):1239.
[30]  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.
[31]  Mahuran D J, Tropak M B, Buttner J D. WO 2009049421, 2009.
[32]  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.
[33]  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.
[34]  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.
[35]  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.
[36]  Valverde A M, Reed S D, Schulman K A. Health Aff., 2012, 31(11): 2528.
[37]  Aymami J, Barril X, Rodríguez-Pascau L, Martinell M. Pharm. Pat. Analyst., 2013, 1: 109.
[38]  Hruska K S, LaMarca M E, Scott C R, Sidransky E. Hum. Mutat., 2008, 29: 567.
[39]  Beutler E, Grabowsli G A. Gaucher disease. in The Metabolic and Molecular Based of Inherited Diseases. 8th ed. NY: McGraw-Hill, 2001. 3635.
[40]  Suzuki Y, Ogawa S, Sakakibara Y. Perspect. Medicin. Chem., 2009, 3: 7.
[41]  Hartl F U, Bracher A, Hayer-Hartl M. Nature, 2011, 475: 324.
[42]  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.
[43]  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.
[44]  Mellor H R, Platt F M, Dwek R A, Butters T D. Biochem. J., 2003, 374: 307.
[45]  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.
[46]  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.
[47]  Yu L, Ikeda K, Kato A, Adachi I, Godin G, Compain P, Martin O, Asano N. Bioorg. Med. Chem., 2006, 14: 7736.
[48]  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.
[49]  Wang G N Twigg G, Butters T D, Zhang S, Zhang L, Zhang L H, Ye X S. Org. Biomol. Chem., 2012, 10: 2923.
[50]  Compain P, Martin O R, Boucheron C, Godin G, Yu L, Ikeda K, Asano N. ChemBioChem., 2006, 7: 1356.
[51]  Goddard-Borger E D, Tropak M B, Yonekawa S, Tysoe C, Mahuran D J, Withers S G. J. Med. Chem., 2012, 55: 2737.
[52]  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.
[53]  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.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133