Developmental Research for Peptides Inducing Membrane Fusion between Liposomes and Cells

药物传递系统（DDS）作为一种靶向细胞的新型治疗手段，受到了广泛的研究。本研究旨在提供诱导脂质体与靶细胞之间膜融合的肽。差示扫描量热法（DSC）用于检测膜融合，因为伴随着融合的磷脂的混合反映在热图上。蜂毒肽（Melittin）是一种蜂毒肽，通过其包含疏水氨基酸和碱性氨基酸两个分离区域的结构，在中性磷脂和酸性磷脂之间表现出脂质体的膜融合。血凝素是流感病毒的一种蛋白，在病毒感染过程中负责膜融合。血凝素中有一个由20个氨基酸组成的区域具有膜融合活性。并且，在含有两种类型脂质体的脂质体系统中研究了模拟20种氨基酸的合成肽的活性。将一种引入谷氨酸的肽添加到磷脂酰胆碱脂质体中。另一种引入赖氨酸的肽被添加到另一种磷脂酰胆碱脂质体中。当使用这些肽时，脂质体之间的静电相互作用在脂质体膜的凝胶和流体阶段有效地诱导了膜融合。在pH 5.0条件下，肽中的谷氨酸发生质子化并变为疏水，在此条件下研究了疏水相互作用对膜融合的影响。在这种情况下，膜融合比静电情况慢得多。然而，在磷脂酰胆碱脂质体中加入胆固醇会提高疏水相互作用诱导的膜融合速率。

Drug delivery system (DDS) is widely studied as a new therapy targeting cells. This research aims to provide peptides that induce membrane fusion between liposomes and a target cell. Differential scanning calorimetry (DSC) is used to detect membrane fusion since mixing of phospholipids accompanied with the fusion is reflected on the thermogram. Melittin, a bee venom peptide, manifested membrane fusion of iposomes between neutral phospholipid and acidic ones through its structure including two separated regions of hydrophobic and basic amino acids. Hemagglutinin is a protein of influenza virus which is responsible for membrane fusion in the process of viral infection. A region composed of 20 amino acids has membrane fusion activity in the hemagglutinin. And, the activity of synthetic peptides that mimic the 20 amino acids are investigated in a liposomal system containing two types of liposomes. One peptide in which glutamic acids are introduced is added to a preparation of phosphatidylcholine liposomes. And the other peptide in which lysines are introduced is added to another preparation of phosphatidylcholine liposomes. When these peptides are used, electrostatic interaction between the liposomes has induced membrane fusion effectively in both gel and fluid phases of liposomal membranes. At pH 5.0, glutamic acids in the peptide are protonated and changed to hydrophobic, and so under this condition effect of hydrophobic interaction on membrane fusion has been investigated. In this case, membrane fusion is much slower compared to the electrostatic case. However, addition of cholesterol to the phosphatidylcholine liposomes raises the rate of membrane fusion induced by hydrophobic interaction.