物理化学学报 >> 2017, Vol. 33 >> Issue (4): 829-835.doi: 10.3866/PKU.WHXB201701062

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拉链型脂肽的温控开关效应

王斯佳,李梦雅,徐首红*(),刘洪来   

  • 收稿日期:2016-12-12 发布日期:2017-03-23
  • 通讯作者: 徐首红 E-mail:xushouhong@ecust.edu.cn
  • 基金资助:
    国家自然科学基金(21276074)

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

Si-Jia WANG,Meng-Ya LI,Shou-Hong XU*(),Hong-Lai LIU   

  • Received:2016-12-12 Published:2017-03-23
  • Contact: Shou-Hong XU E-mail:xushouhong@ecust.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(21276074)

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: 亮氨酸, 拉链型脂肽, 脂质体, 温敏性, 药物载体

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: Leucine, Zipper-structured lipopeptide, Liposome, Thermo-sensitivity, Drug carrier

MSC2000: 

  • O647