| Project/Area Number |
16H04180
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bio-related chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
Hojo Hironobu 大阪大学, 蛋白質研究所, 教授 (00209214)
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| Co-Investigator(Renkei-kenkyūsha) |
SATO Takeshi 京都薬科大学, 一般教育分野, 教授 (90403013)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | カベオリン / 化学合成 / 特異的修飾 / ライゲーション法 / ペプチドチオエステル / 固相合成法 / 膜タンパク質 / 翻訳後修飾 / チオエステル法 / セグメント縮合 |
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| Outline of Final Research Achievements |
In this study, the chemical synthesis of caveolin, which is an important protein for the formation of caveola, was performed. To accomplish the synthesis, the entire sequence was divided into 5, and each peptide segment was prepared by the solid-phase method. As caveolin is partly inserted in lipid bilayer, it retains highly hydrophobic character. Therefore, the O-acylisopeptide structure, which is efficient to increase the solubility of the peptide segment, was introduced to the C-terminal segments. As a result, all the segments could be synthesized and purified by high-performance liquid chromatography. The obtained segments were then condensed by our segment condensation method (The thioester method) and the polypeptide with the entire sequence of caveolin was obtained. The protecting groups at the side chain SH group of Cys residues were then removed and the palmitoyl groups were introduced. Finally, all the protecting groups were removed to obtain the desired caveolin.
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| Academic Significance and Societal Importance of the Research Achievements |
生体内では絶えず細胞内外で物質、情報がやり取りされている。細胞膜上での物質の取り込み方法の一つとして、カベオラと呼ばれるくぼみを利用する方法がある。カベオラの細胞質側には、カベオリンが集積している。しかし、カベオリンが集積すればくぼみができるのか等、カベオラによる物質取り込みの詳細は不明である。カベオリンの変異は、がん等種々の疾患への関与が示唆されており、カベオリンの詳細な機能解明が望まれている。しかし、カベオリンは膜に存在するため、機能解析に必要な高純度の試料の調製が困難であった。本研究でカベオリンの化学合成法が確立できたことから、今後カベオリンの機能研究に大きく貢献できるものと期待される。
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