研究生: |
王曼卉 Wang, Man-Hui |
---|---|
論文名稱: |
利用核磁共振技術探討人類interleukin-1α與suramin的複合物結構 Study on complex structure between human interleukin-1α and suramin by NMR |
指導教授: |
余靖
Yu, Chin |
口試委員: | |
學位類別: |
碩士 Master |
系所名稱: |
理學院 - 化學系 Department of Chemistry |
論文出版年: | 2010 |
畢業學年度: | 98 |
語文別: | 中文 |
論文頁數: | 60 |
中文關鍵詞: | 核磁共振 |
相關次數: | 點閱:1 下載:0 |
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摘要
IL-1α(介白素,Interleukin-1α)為一具有多樣生物活性的訊息傳遞分子,其經由非典型路徑分泌出細胞後,會與細胞表面的受器作用並引發訊息傳遞。如引起發燒、刺激肝臟製造急性蛋白、增大淋巴細胞的回應、誘發關節退化、增加骨髓細胞數目等等。且IL-1α也是造成類風濕性關節炎與退化性關節炎的主因之一,其在人體中扮演了重要的角色。
□已有研究指出,Suramin藉由干擾IL-1α與其受器的結合而抑制軟骨被破壞,進而減緩類風濕性關節炎的症狀。在本篇論文中,我們探討一個有機化合物Suramin藉由與IL-1α結合干擾蛋白質與其受器的交互作用,最後達到抑制軟骨被破壞的效果
□首先,我們利用1H-15N HSQC擾動實驗來找出IL-1α與Suramin作用的胺基酸以描繪出結合位置。由穩定態變溫實驗發現 Suramin能夠穩定IL-1α分子。此外,為了瞭解結合態中IL-1α與Suramin的相對位置與方向性,我們使用三維共振的NMR實驗;包括HNCA、HCCONH、CCONH 、HCCH-TOCSY 與13C-edited及13C &15N-filtered的實驗來得到骨架與側鏈的資訊,利用HADDOCK對IL-1α與Suramin進行分子對應模擬。此計算結果說明Suramin如何影響IL-1α與IL-1RΙ的結合。
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