| Project/Area Number |
06558116
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
OHKI Kazuo Tohoku University, Graduate School of Science, Department of Physics, Professor, 大学院・理学研究科, 教授 (80115394)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Toshihide Tohoku University, Graduate School of Science, Department of Physics, Associate, 大学院・理学研究科, 助教授 (60162004)
OHBA Tetsuhiko Tohoku University, Graduate School of Science, Department of Physics, Research s, 大学院・理学研究科, 助手 (10250664)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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