| Item type |
学位論文 / Thesis or Dissertation(1) |
| 公開日 |
2018-09-28 |
| タイトル |
|
|
タイトル |
新規フォトクロミック阻害剤を利用した有糸分裂キネシンEg5の高効率光制御に関する研究 |
|
言語 |
ja |
| タイトル |
|
|
タイトル |
Study on the highly efficient photoregulation of mitotic kinesin Eg5 using novel photo-chromic inhibitor |
|
言語 |
en |
| 言語 |
|
|
言語 |
jpn |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
|
資源タイプ |
doctoral thesis |
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 著者 |
貞包, 慧
Sadakane, Kei
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Living cell is composed of millions of densely packed biomolecules that perform so many tasks to constitute life. Recently, the structure and function of the biomolecules that have a key role in cell motility have been clarified. ATP driven molecular motor kinesin is one of the functional biomolecules and have roles in mitosis, meiosis and transport of cellular cargo, such as in axonal transport. Kinesin Eg5 is a microtubule plus-end directed homotetrameric molecular motor that is essential for the formation of bipolar spindle during eukaryotic cell division. Interestingly, Eg5 have a unique pocket at near the ATP binding site at where specific inhibitors of the Eg5 binds. S-trityl-L-cysteine (STLC) and monastrol are well known as potent Eg5 specific inhibitors. Inhibition of Eg5 with the inhibitors results in inducing cytostasis and apoptosis. In this study, novel photochromic inhibitors of Eg5 composed of spiropyran or azobenzene derivatives were designed and synthesized in order to control the function of Eg5 photo-reversibly with high efficiency. The inhibitors exhibited photoisomerization upon ultraviolet and visible light irradiations. The Eg5 inhibitors composed of single spiropyran derivative exhibited low efficient photoregulation. On the other hand, the compound (S)-2, 3-dispiropyran propionic acid (DSPPA) which contains two photochromic spiropyran moieties showed singnificant alteration of inhibitory activity accompanied by photo-isomerization. Furthermore, the function of Eg5 was regulated photo-reversibly by the double azobenezene derivative, 2, 3-bis[(2,5-dioxo-1-{4-[(E)-2-phenyldiazen-1-yl]phenyl}pyrrolidin-3-yl) sulfanyl] butanedioic acid (BDPSB) with extremely high efficiency. It was demonstrated that the novel Eg5 inhibitors containing double photochromic molecules enable highy efficient photoregulation of mitotic kinesin Eg5. |
| 学位名 |
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|
学位名 |
博士（工学） |
| 学位授与機関 |
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|
学位授与機関名 |
創価大学 |
| 学位授与年月日 |
|
|
学位授与年月日 |
2018-09-15 |
| 学位授与番号 |
|
|
学位授与番号 |
甲第161号 |
| 著者版フラグ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
kogakukenkyuka_Sadakane-Kei(1).pdf (600.9 kB)
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