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Developmental Research for Peptides Inducing Membrane Fusion between Liposomes and Cells

诱导脂质体与细胞膜融合的肽的开发研究

基本信息

批准号：
06558116
负责人：
OHKI Kazuo
金额：
$ 5.5万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06558116/
关键词：
membrane fusion carrier liposome peptides DSC drug delivery system target cell phase transition phospholipids 担体リポソームリポソーム蛍光測定細胞医用工学

项目摘要

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.

药物传递系统（DDS）作为一种新型的靶向治疗手段，受到了广泛的研究.本研究旨在提供诱导脂质体和靶细胞之间的膜融合的肽。差示扫描量热法（DSC）用于检测膜融合，因为伴随融合的磷脂混合反映在热谱图上。蜂毒肽（Melittin）是一种由碱性氨基酸和疏水性氨基酸组成的两个分离区域，其结构表现为中性磷脂和酸性磷脂之间的脂质体膜融合。血凝素是流感病毒的一种蛋白质，在病毒感染过程中负责膜融合。由20个氨基酸组成的区域在血凝素中具有膜融合活性。并且，在含有两种类型脂质体的脂质体系统中研究模拟20种氨基酸的合成肽的活性。将其中引入谷氨酸的一种肽添加到磷脂酰胆碱脂质体制剂中。并将其中引入赖氨酸的另一种肽加入到磷脂酰胆碱脂质体的另一种制剂中。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相和流体相中有效地诱导膜融合。在pH5.0时，肽中的谷氨酸被质子化并变为疏水性的，因此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，向磷脂酰胆碱脂质体中添加胆固醇会提高疏水性相互作用诱导的膜融合速率。