2019 Fiscal Year Final Research Report
Development of the tumor-selective necrosis inducers and anti-leukemia agents
| Project/Area Number |
17K08383
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Sojo University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | ネクローシス / ペプチド / 腫瘍ターゲティング / 白血病 |
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| Outline of Final Research Achievements |
To identify the molecular mechanism that underlies the necrotic process of leukemia cells with new peptide Tat-Ram13, we carried out the identification of Tat-Ram13 peptide-binding proteins by several approaches.
First, we prepared the Ram13-peptide agarose and tried to pick up the Ram13 binding protein from the Jurkat-T cell lysate. 2D PAGE analysis revealed that the major-specific spot was observed as approximately 50 kDa. Next, we transfected the shRNA library plasmid into Jurkat-T cells and prepared the surface membrane/nuclear protein knockdown cells. These cells were treated with Tat-Ram13 peptide and collected survived cells. DNA sequencing analysis gave us several high-frequency molecules and real-time PCR analysis revealed the STAP-2, a signal-transducing adaptor 50 kDa protein, is expressed in the Tat-Ram13-sensitive leukemia cells.
These data suggest that STAP-2 may a key molecule of Tat-Ram13-inducing necrotic cell death.
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| Free Research Field |
生体機能化学
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| Academic Significance and Societal Importance of the Research Achievements |
Tat-Ram13ペプチドは、白血病細胞に選択的にネクローシスを誘導するユニークな特性を有している。その作用メカニズムを明らかにすることは、がん治療における新規概念に基づく創薬戦略、及びネクローシス誘導型抗悪性腫瘍薬の開発に役立つと考えられる。
本研究において機能性配列Ram13の結合分子を絞り込み、同定まであと一歩のところまで到達した。本研究で見出したRam13結合候補分子は免疫系での多機能タンパク質として知られている分子であり、非アポトーシス細胞死との関連性を明らかにすることは興味深いと考えられる。
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