| Project/Area Number |
12672151
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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 |
医薬分子機能学
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| Research Institution | Nagoya University |
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Principal Investigator |
OHKURA Kazuto Graduate School of Bioagricultural Sciences, Nagoya University Assistant Professor, 大学院・生命農学研究科, 助手 (00242850)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAMUNE Hideaki Faculty of Engineering, University of Tokushima Associate Professor, 工学部, 助教授 (40189163)
HORI Hitoshi Faculty of Engineering, University of Tokushima Professor, 工学部, 教授 (90119008)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | cytolysin / targeting / infection / コレステロール |
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| Research Abstract |
Intermedilysin (ILY), a human specific cytolysin secreted by Streptococcus intermedius, is a member of the gene of SLO-family cytolysin (SFC), but differs by exhibiting a low affinity to cholesterol (CHL) in addition to human specificity. We modeled ILY molecule using perfringolysin O (PFO) X-ray data, and observed four domain (domain 1 〜 domain 4) in the molecule. From the analysis of ILY model, the domain 4 seems to be the human cell membrane associated region. Especially, extended-NTD sequence at ILY C-terminal appeared an important factor for human specific cytolysis. Indeed, the NTD-deleted ILY mutant (ΔNTD-ILY) decreased the hemolytic activity for human erythrocytes. Then we considered that the C-terminal NTD should be concerning with the cluster formation on the human cell membrane.
Moreover we constructed the antiCEA-antibody conjugated ILY domain4 (antiCEA-ILY4D), and examined the cell delivery system. AntiCEA-ILY4D bind to human erythrocyte (ET) membrane easily, and this ET-AntiCEA-ILY4D module recognized CEA-positive TT cell. Now we are improving these targeting modules.
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