一种新型还原敏感型阳离子寡肽脂质的合成及其在模拟细胞质还原性环境中的降解动力学

目的：设计合成一种新型还原敏感型阳离子寡肽脂质材料，以期由其制得的脂质体可用作核酸药物载体在细胞质还原性环境促发下降解而释放药物。方法：以胱胺为原料引入二硫键，合成还原敏感型阳离子寡肽脂质材料H-SS-E2C14，并用其制备还原敏感型阳离子寡肽脂质体H-SS-E2C14-L；同时，以半胱胺为原料合成H-SS-E2C14 的降解产物CS-E2C14，且采用HPLC 法定量考察H-SS-E2C14在模拟细胞质还原性环境中的降解动力学。结果：合成的H-SS-E2C14 在模拟细胞质还原性环境中的24 h 累积降解率约为70%。结论：H-SS-E2C14-L 有望成为一种理想的基因药物载体。

Synthesis of a Novel Redox-responsive Cationic Oligopeptide Lipid and Its Degradation Dynamics in a Simulated Cytoplasmic Reducing Environment

Objective: To design and synthesize a novel redox-responsive cationic oligopeptide lipid material, which is used to prepare the liposome as a nucleic acid drug carrier that can be degraded, releaseing nucleic acid drugs in the cytoplasmic reducing environment. Methods: Using cystamine as disulfide bond donor, H-SS-E2C14, a redox-responsive cationic oligopeptide lipid material, was synthesized and it was used to prepare H-SSE2C14-L, a redox-responsive cationic oligopeptide liposome. Meanwhile, the degradation product of H-SS-E2C14 was synthesized with cysteamine as the starting material. The degradation kinetics of H-SS-E2C14 in a simulated cytoplasmic reducing environment was investigated quantitatively by HPLC. Results: The 24 h-accumulative degradation rate of the synthesized H-SS-E2C14 was about 70% in the simulated cytoplasmic reducing environment. Conclusion: The prepared H-SS-E2C14-L has the potential to be an ideal gene drug carrier.