两种抗粘附活性乳糖苷及其荧光和生物素标记物的合成

doi:10.5246/jcps.2011.04.040

两种抗粘附活性乳糖苷及其荧光和生物素标记物的合成

李庆, 赵岳涛, 孟祥豹, 严婷婷, 李树春, 黄河清, 赵智辉^*, 李中军^*

1. 北京大学医学部天然药物及仿生药物国家重点实验室; 药学院化学生物学系, 北京 100191
2. 南京师范大学江苏省分子与药物生物技术学重点实验室; 生命科学院, 江苏南京 210046

收稿日期:2011-03-16 修回日期:2011-05-20 出版日期:2011-07-01 发布日期:2011-07-01
通讯作者: 赵智辉*, 李中军*

Synthesis of two multivalent lactosides with anti-adhesive activity and their fluorescein-labeled and biotin-labeled derivatives

Qing Li, Yue-Tao Zhao, Xiang-Bao Meng, Ting-Ting Yan, Shu-Chun Li, He-Qing Huang, Zhi-Hui Zhao^*, Zhong-Jun Li^*

1. State Key Laboratory of Natural and Biomimetic Drugs; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210046, China

Received:2011-03-16 Revised:2011-05-20 Online:2011-07-01 Published:2011-07-01
Contact: Zhi-Hui Zhao*, Zhong-Jun Li*

摘要/Abstract

摘要： 白细胞与内皮细胞的粘附在炎症相关的疾病中起着重要作用, 前期研究发现的多价乳糖苷可以很好地抑制该过程而发挥抗炎活性。我们以2-氨基-1,3-丙二醇、谷氨酸为连接臂, 采用收敛法合成了二价乳糖苷An-2及四价乳糖苷Gu-4, 这两个化合物显示了良好的抗粘附活性, 对重症烧伤休克大鼠具有较好的治疗效果。利用An-2及Gu-4的荧光标记物Yan-2和YGu-4进行的抗粘附机制研究表明, 多价乳糖苷的作用靶点是白细胞上的整合素CD11b。本文将报道这两种新的多价乳糖苷及其荧光和生物素标记物的合成。

关键词: 抗粘附, 生物素, 荧光素, 多价乳糖, 合成

Abstract:

Adhesion of leukocytes to endothelium plays an important role in inflammation-associated diseases. Our previous studies showed that multivalent lactosides were able to inhibit this process. Using 2-azide-1,3-propandiol and glutamic acid as spacers, we synthesized divalent lactoside An-2 and tetravalent lactoside Gu-4 by means of convergent method. These two compounds displayed high anti-adhesive activity and showed therapeutic effect in rats with severe burn shock. In addition, investigation of the anti-adhesion biological mechanism using labeled compounds YAn-2 and YGu-4 demonstrated that the target of multivalent lactosides was CD11b, the β2 integrin subunit, on the surface of leukocytes. In this paper, the synthesis of these two new multivalent lactosides as well as their fluorescein-labeled and biotin-labeled compounds is reported.

Key words: Anti-adhesion, Biotin, Fluorescein, Multivalent-lactosides, Synthesis

中图分类号:

R916.41

Supporting:

Foundation items: National Natural Science Foundation of China (Grant No. 90713004) and Ministry of Science and Technology of China (Grant No. 2009ZX09103044, 2009ZX09301-010).
^*Corresponding author. Tel.: 86-10-82801714; Fax: 86-10-82805496;

E-mail: zjli@bjmu.edu.cn (Zhong-Jun Li); zhaozhihui_1964@yahoo.com.cn (Zhi-Hui Zhao)

李庆, 赵岳涛, 孟祥豹, 严婷婷, 李树春, 黄河清, 赵智辉^*, 李中军^*.

两种抗粘附活性乳糖苷及其荧光和生物素标记物的合成

[J]. , DOI: 10.5246/jcps.2011.04.040.

Qing Li, Yue-Tao Zhao, Xiang-Bao Meng, Ting-Ting Yan, Shu-Chun Li, He-Qing Huang, Zhi-Hui Zhao^*, Zhong-Jun Li^* . Synthesis of two multivalent lactosides with anti-adhesive activity and their fluorescein-labeled and biotin-labeled derivatives[J]. , DOI: 10.5246/jcps.2011.04.040.

参考文献

[1] Wang, X.D.; Zhao, H.; Andersson, R. J. Proteome Res. 2004, 3, 921-929.
[2] Zhu, G.D.; Arendsen, D.L.; Gunawardana, I.W.; Boyd, S.A.; Stewart, A.O.; Fry, D.G.; Cool, B.L.; Kifle, L.; Schaefer, V.; Meuth, J.; Marsh, K.C.; Kempf-Grote, A.J.; Kilgannon, P.; Gallatin, W.M.; Okasinski, G.F. J. Med. Chem. 2001, 44, 3469-3487.
[3] Kaila, N.; Janz, K.; DeBernardo, S.; Bedard, P.W.; Camphausen, R.T.; Tam, S.; Tsao, D.H.H.; Keith, J.C.Jr.; Nickerson-Nutter, C.; Shilling, A.; Young-Sciame, R.; Wang, Q. J. Med. Chem. 2007, 50, 21-39.
[4] Signore, A.; Mather, S.J.; Piaggio, G.; Malviya, G.; Dierckx, R.A. Chem. Rev. 2010, 110, 3112-3145.
[5] Nakae, H.; Endo, S.; Yamada, Y.; Inada, K. Burns. 2000, 26, 139-144.
[6] Muller, W.A. Trends Immunol. 2003, 24, 326-333.
[7] Geng, J.G.; Chen, M.; Chou, K.C. Curr. Med. Chem. 2004, 11, 2153-2160.
[8] Khan, R.; Kirschenbaum, L.A.; LaRow, C.; Berna, G.; Griffin, K.; Astiz, M.E. Shock. 2010, 33, 242-246.
[9] Li, Q.; Cai, M.S.; Li, Z.J. Chem. J. Chin. Univ. 2000, 21, 70-73.
[10] Zhang, W.; Li, Q.; Meng, X.B.; Zhao, Z.H.; Li, Z.J. J. Chin. Pharm. Sci. 2007, 16, 128-131.
[11] Meng, X.B.; Yang, L.D.; Li, H.; Li, Q.; Cheng, T.M.; Cai, M.S.; Li, Z.J. Carbohydr. Res. 2002, 337, 977-981.
[12] Mitsuoka, C.; Sawada-Kasugai, M.; Ndo-Furui, K.; Izawa, M.; Nakanishi, H.; Nakamura, S.; Ishida, H.; Kiso, M.; Kannagi, R. J. Biol. Chem. 1998, 273, 11225-11233.
[13] Kaila, N.; Thomas, B.E. Med. Res. Rev. 2002, 22, 566-601.
[14] Thrnbull, W.B.; Stoddart, J.F. Rev. Mol. Biotechnol. 2002, 90, 231-255.
[15] Rosen, B.M.; Wilson, C.J.; Wilson, D.A.; Peterca, M.; Imam, M.R.; Percec, V. Chem. Rev. 2009, 109, 6275-6540.
[16] Yin, Z.J.; Li, Q.; Meng, X.B.; Li, Z.J. Carbohydr. Res. 2007, 342, 2729-2734.
[17] Zanini, D.; Roy, R. J. Org. Chem. 1998, 63, 3486-3491.
[18] Lindhorst, T.K.; Kieburg, C. Angew. Chem. Int. Ed. Engl. 1996, 35, 1953-1956.
[19] Zhao, Z.H.; Li, Q.; Hu, J.; Li, Z.J.; Liu, J.H.; Liu, A.H.; Deng, P.; Zhang, L.; Gong, X.W.; Zhao, K.S.; Zhang, S.Q.; Jiang, Y. Glycoconj. J. 2009, 26, 173-188.