拉链型脂肽的温控开关效应

引用本文: 王斯佳, 李梦雅, 徐首红, 刘洪来. 拉链型脂肽的温控开关效应[J]. 物理化学学报, 2017, 33(4): 829-835. doi: 10.3866/PKU.WHXB201701062 shu

Citation: WANG Si-Jia, LI Meng-Ya, XU Shou-Hong, LIU Hong-Lai. Thermo-Controlled On-Off Switch of Zipper-Structured Lipopeptides[J]. Acta Physico-Chimica Sinica, 2017, 33(4): 829-835. doi: 10.3866/PKU.WHXB201701062 shu

拉链型脂肽的温控开关效应

华东理工大学化学与分子工程学院, 结构可控先进功能材料及其制备教育部重点实验室, 上海 200237
基金项目:
国家自然科学基金（21276074）资助项目

摘要: 亮氨酸拉链型脂肽是由两条肽链以螺旋结构依靠疏水作用并列结合形成的二聚体，当温度升至其相变温度时，其螺旋结构解旋继而变为无序链状结构。利用该类脂肽的温敏性能，本文设计、合成得到一组具有温敏性的拉链型脂肽，将其与磷脂混合制备温敏性脂质体。用圆二色谱测定磷脂双分子层上脂肽的二级结构，动态光散射测定脂肽-脂质体的粒径及电位；荧光偏振法测定脂质体膜的流动性；采用紫外分光光度计考察阿霉素（DOX）在37.0、45.0℃下的释放行为。结果表明，含有脂肽的脂质体具备较好的温敏性，胆固醇含量、脂质体膜的流动性，对脂肽的温控开关效应有一定的影响。脂肽-脂质体作为一种新型的温敏性药物载体展现了其较好的应用前景。

关键词:

English

Thermo-Controlled On-Off Switch of Zipper-Structured Lipopeptides

Key Laboratory for Advanced Materials and Institute of Fine Chemicals of the Education Ministry of China, College of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China
Received Date: 12 December 2016
Revised Date: 06 January 2017
Available Online: 06 January 2017
Fund Project:
The project was supported by the National Natural Science Foundation of China (21276074).

Abstract: The leucine zipper lipopeptide is a dimer composed of two lipopeptides with α-helical structures that interact through hydrophobic forces. When heated to its phase transition temperature, the helixes unwind and form a disordered conformation. Based on the thermo-sensitivity of these leucine zipper lipopeptides, we designed and synthesized a series of zipper-structured lipopeptides and then mixed them with lipids to form thermo-sensitive hybrid liposomes. Circular dichroism was used to investigate the secondary structure of the lipopeptides anchored in the liposomal bilayer. Dynamic light scattering measurements were used to assess the diameters and zeta potentials of the liposomes. Fluorescence polarization was measured to study the fluidity of the liposomal bilayer. An ultraviolet spectrophotometer was used to stimulate Doxorubicin (DOX) release in vitro at 37.0 and 45.0℃. We found that Lp-Lipo (hybrid of lipopeptide and liposome) displayed higher thermosensitivity than pure liposome. The cholesterol content and fluidity of the liposomal bilayer affected the thermocontrolled on-off switch of the lipopeptides. Lp-Lipo shows great potential as a novel thermo-sensitive drug carrier.

Key words:

1. [1]
  Fernandes, R. S.; Silva, J. O.; Monteiro, L. O.; Leite, E. A.; Cassali, G. D.; Rubello, D.; Cardoso, V. N.; Ferreira, L. A.; Oliveira, M. C.; de Barros, A. L. Biomed. Pharmacother 2016, 84, 252. doi: 10.1016/j.biopha.2016.09.032
2. [2]
  Ran, R.; Middelberg, A. P.; Zhao, C. X. Colloids Surf. B 2016, 148, 402. doi: 10.1016/j.colsurfb.2016.09.016
3. [3]
  Liang, X. F.; Hu, J. Y.; Chen, F. H.; Li, Z. H.; Chang, J. Acta Phys. -Chim. Sin. 2012, 28, 897. [梁晓飞, 胡晶莹, 陈复华, 李宗海, 常津. 物理化学学报, 2012, 28, 897.] doi: 10.3866/PKU.WHXB201202091
4. [4]
  Araki, T.; Ogawara, K.; Suzuki, H.; Kawai, R.; Watanabe, T.; Ono, T.; Higaki, K. J. Controlled Release 2015, 200, 106. doi: 10.1016/j.jconrel.2014.12.038
5. [5]
  Liu, D. Y.; Wang, S. J.; Xu, S. H.; Liu, H. L. Langmuir 2017, 33 (4), 1004. doi: 10.1021/acs.langmuir.6b03051
6. [6]
  Zhao, Y.; Ren, W.; Zhong, T.; Zhang, S.; Huang, D.; Guo, Y.; Yao, X.; Wang, C.; Zhang, W. Q.; Zhang, X.; Zhang, Q. J. Controlled Release 2016, 222, 56. doi: 10.1016/j.jconrel.2015.12.006
7. [7]
  Vila-Caballer, M.; Codolo, G.; Munari, F.; Malfanti, A.; Fassan, M.; Rugge, M.; Balasso, A.; de Bernard, M.; Salmaso, S. J. Controlled Release 2016, 238, 31. doi: 10.1016/j.jconrel.2016.07.024
8. [8]
  Tai, L. A.; Wang, Y. C.; Yang, C. S. Nitric Oxide-Biol. Ch. 2010, 23, 60. doi: 10.1016/j.niox.2010.04.003
9. [9]
  Zhou, W. T.; An, X. Q.; Wang, J. Z.; Shen, W. G.; Chen, Z. Y.; Wang, X. Y. Colloids Surf. A 2012, 395, 225. doi: 10.1016/j.colsurfa.2011.12.034
10. [10]
  Safra, T.; Muggia, F.; Jeffers, S.; Tsao-Wei, D. D.; Groshen, S.; Lyass, O.; Henderson, R.; Berry, G.; Gabizon, A. Ann. Oncol. 2000, 11, 1029. doi: 10.1023/a:1008365716693
11. [11]
  Jang, H. J.; Kim, Y. K.; Huh, H.; Min, D. H. ACS Nano 2014, 8, 467. doi: 10.1021/nn404833b
12. [12]
  O'Gorman, C.; Sasiadek, W.; Denieffe, S.; Gooney, M. Clin. J. Oncol. Nurs. 2014, 18, E37. doi: 10.1188/14.cjon.e37-e44
13. [13]
  Sancar, A.; Lindsey-Bolt, L. A.; Gaddameedhi, S.; Selby, C. P.; Ye, R.; Chiou, Y. Y.; Kemp, M. G.; Hu, J. C.; Lee, J. H.; Ozturk, N. Biochemistry 2015, 54, 110. doi: 10.1021/bi5007354
14. [14]
  Lai, J. R.; Fisk, J. D.; Weisblum, B.; Gellman, S. H. J. Am. Chem. Soc. 2004, 126, 10514. doi: 10.1021/ja047710f
15. [15]
  Shen, W.; Lammertink, R. G. H.; Sakata, J. K.; Kornfield, J. A.; Tirrell, D. A. Macromolecules 2005, 38 (9), 3909. doi: 10.1021/ma048348s
16. [16]
  Mason, J. M.; Hagemann, U. B.; Arndt, K. M. Biochemistry 2009, 48, 10380. doi: 10.1021/bi901401e
17. [17]
  Al-Ahmady, Z. S.; Al-Jamal, W. T.; Bossche, J. V.; Bui, T. T.; Drake, A. F.; Mason, A. J.; Kostarelos, K. ACS Nano 2012, 6, 9335. doi: 10.1021/nn302148p
18. [18]
  Lendel, C.; Bolognesi, B.; Wahlstrom, A.; Dobson, C. M.; Graslund, A. Biochemistry 2010, 49, 1358. doi: 10.1021/bi902005t
19. [19]
  Han, S. H.; Lee, M. K.; Lim, Y. B. Biomacromolecules 2013, 14, 1594. doi: 10.1021/bm400233x
20. [20]
  Kotova, E. A.; Kuzevanov, A. V.; Pashkovskaya, A. A.; Antonenko, Y. N. Biochim. Biophys. Acta 2011, 1808, 2252. doi: 10.1016/j.bbamem.2011.05.018
21. [21]
  Randles, E. G.; Bergethon, P. R. Langmuir 2013, 29, 1490. doi: 10.1021/la303526k
22. [22]
  Soto-Arriaza, M. A.; Olivares-Ortega, C.; Lissi, E. A. J. Colloid Interface Sci. 2012, 385, 48. doi: 10.1016/j.jcis.2012.07.028
23. [23]
  Karolin, J.; Geddes, C. D. J. Phys. Chem. Lett. 2015, 6, 918. doi: 10.1021/acs.jpclett.5b00185
24. [24]
  Meijer, J. T.; Roeters, M.; Viola, V.; Löwik, D.W. P. M.; Vriend, G.; van Hest, J. C. M. Langmuir 2007, 23, 2058. doi: 10.1021/la0625345
25. [25]
  Forns, P.; Lauer-Fields, J. L.; Gao, S.; Fields, G. B. Biopolymers 2000, 54, 531. doi: 10.1002/1097-0282(200012)54:7<531::AIDBIP60>3.0.CO;2-X
26. [26]
  Khan, D. R.; Rezler, E. M.; Lauer-Fields, J.; Fields, G. B. Chem. Biol. Drug Des. 2008, 71, 3. doi: 10.1111/j.1747-0285.2007.00610.x
27. [27]
  Ohvo-Rekilä, H.; Ramstedt, B.; Leppimäki, P.; Peter Slotte, J. Prog. Lipid Res. 2002, 41, 66. doi: 10.1016/S0163-7827(01)00020-0
28. [28]
  Gao, W. Y.; Chen, L.; Wu, F. G.; Yu, Z.W. Acta Phys. -Chim. Sin. 2008, 24, 1149. [高文颖, 陈琳, 吴富根, 尉志武. 物理化学学报, 2008, 24, 1149.] doi: 10.1016/S1872-1508(08)60050-9

扫一扫看文章

计量

PDF下载量: 1
文章访问数: 880
HTML全文浏览量: 81

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

拉链型脂肽的温控开关效应

English

Thermo-Controlled On-Off Switch of Zipper-Structured Lipopeptides

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

计量

通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

拉链型脂肽的温控开关效应

English

Thermo-Controlled On-Off Switch of Zipper-Structured Lipopeptides

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

计量

文章相关

通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs