| Project/Area Number |
10680570
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bioorganic chemistry
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| Research Institution | Nagasaki University |
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Principal Investigator |
AOYAGI Haruhiko Nagasaki University, Department of Applied Chemistry, Professor, 工学部, 教授 (80037267)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | amphiphilic peptide / model peptide / phosphilipid membrane / antibacterial activity / lectin / hemolytic activity / nucleic acid carrier / galactose modification / 膜破壊能 / コンジュゲート / DNA細胞内移入 / アミノ酸置換アナログ / β構造 / αヘリシティ |
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| Research Abstract |
Peptide contributes not only elucidation of action mechanism and structure-function relationship but also to drug design and modeling of functional materials. We have studied the structure-function relationship of antibacterial peptides, pleurocidin (Ple) and bactenecin 5 (Bac 5), effect of chemical modification of hemolytic lectin CEL-III on its cytotoxic activity, and use of cationic amphiphilic peptides as gene carriers into cells. 1) Using some amino acid-substituted Ple analogs, we examined their interaction with lipid and cell membranes. Balance of hydrophobicity and positive charge of Ple was found to be important for antibacterial activity. About Bac 5, it became clear that a certain chain length in the central repeating region is essential for antibacterial activity and the strongly cationic N-terminal portion enhances the activity. 2) By modification of the side chains of Glu and Asp residues in CEL-III with Gly-OMe, not only hemolytic activity but also carbohydrate-binding and agglutinative activities were greatly decreased, suggesting that carboxylic residues at the binding or near site are modified and the binding with carbohydrate would be interrupted. 3) Cationic amphiphilic peptides were modified with galactose, and their DNA transfer ability was evaluated using a human hepatoma cell line. Higher ability was observed with increasing galactose residues. Furthermore, we found that internalization of the DNA-galactose-modified peptide complexes is caused by the receptor-mediated endocytosis.
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