Key Laboratory for Advanced Materials and School of Chemistry and Molecular Engineering, East China University of Science and Technology , Shanghai, 200237, China.
Langmuir. 2017 Feb 14;33(6):1478-1485. doi: 10.1021/acs.langmuir.6b04080. Epub 2017 Jan 31.
A zipper-structured lipopeptide is expected to play a role of "intelligent valve" in the lipid bilayer. In this paper, a series of zipper-structured lipopeptides have been designed for preparing thermocontrollable hybrid liposomes. Their conformational transition as a function of temperature in lipid bilayer has been investigated for understanding the influences of molecular structure and bilayer property on biofunction. The melting temperatures T of the lipopeptides have been found to depend on their molecular structures. When the lipopeptides have been doped in bilayer, an increase of size of alkyl chain increases the stability of the α-helix resulting in a decrease in fluidity of lipid bilayer. However, an increase of amino groups at N-terminal is found to decrease the stability of the spatial structure. The thermocontrollability of the "valve" in lipid bilayer is confirmed by drug release experiments under different temperatures. Meanwhile, effects of bilayer properties on the thermosensitivity of lipopeptides have also been investigated. Results show the T of lipopeptide doped in bilayer decreases with the increase of membrane fluidity. Furthermore, the reversibility of the thermocontrolled "valve" is also proven by release drug under intermittent temperatures. It could be concluded that the molecular structure of the lipopeptide, as well as the property of bilayer, give great influence on the biofunction of the hybrid liposomes.
拉链结构脂肽有望在脂质双分子层中充当“智能阀”的角色。本文设计了一系列拉链结构脂肽，用于制备热控混合脂质体。研究了其在脂质双层中随温度的构象转变，以了解分子结构和双层性质对生物功能的影响。发现脂肽的熔融温度 T 取决于它们的分子结构。当脂肽掺杂在双层中时，烷基链长度的增加会增加 α-螺旋的稳定性，从而降低脂质双层的流动性。然而，在 N 端增加氨基基团会降低空间结构的稳定性。通过在不同温度下的药物释放实验证实了脂质双层中“阀”的热控能力。同时，还研究了双层性质对脂肽热敏感性的影响。结果表明，掺杂在双层中的脂肽的 T 随膜流动性的增加而降低。此外，通过间歇性温度下的药物释放也证明了热控“阀”的可逆性。可以得出结论，脂肽的分子结构以及双层的性质对混合脂质体的生物功能有很大的影响。
