Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China.
Faraday Discuss. 2018 Sep 28;209(0):149-159. doi: 10.1039/c8fd00009c.
Despite the fact that a large number of synthetic channels have been developed in the last three decades, few of them can function in mammalian cell membranes because of their weak membrane insertion abilities. This study describes a tubular molecule with terminal positively charged amino groups that displays a strong ability to insert into lipid bilayers composed of phosphatidylcholine and consequently forming unimolecular transmembrane channels. It has been demonstrated that the insertion of the channel into the phosphatidylcholine bilayers was driven by the electrostatic interaction between the positively charged amino groups of the channel molecules and the negatively charged phosphate groups of the lipid molecules. The high affinity of the channels for lipid bilayers led to efficient mammalian cell membrane insertion. The channels showed high effective activity against HepG2 cancer cells at concentrations above 5.1 μM.
尽管在过去的三十年中已经开发出了大量的合成通道，但由于它们插入细胞膜的能力较弱，很少有通道能够在哺乳动物的细胞膜中发挥作用。本研究描述了一种具有末端正电荷氨基的管状分子，它具有很强的插入由磷脂酰胆碱组成的脂质双层的能力，从而形成单分子跨膜通道。已经证明，通道插入磷脂双层是由通道分子的正电荷氨基与脂质分子的负电荷磷酸基团之间的静电相互作用驱动的。通道对脂质双层的高亲和力导致其能够有效地插入哺乳动物细胞膜。该通道在浓度高于 5.1 μM 时对 HepG2 癌细胞表现出高的有效活性。
