研究生: |
曾維寬 Tseng, Wei-Kuan |
---|---|
論文名稱: |
利用新策略設計出具有穩定性之白細胞介素2 Novel strategy to design stable Interleukin-2 |
指導教授: |
蘇士哲
Sue, Shih-Che |
口試委員: |
鄭惠春
Cheng, Hui-Chun 吳昆峯 Wu, Kuen-Phon |
學位類別: |
碩士 Master |
系所名稱: |
生命科學暨醫學院 - 生物資訊與結構生物研究所 Institute of Bioinformatics and Structural Biology |
論文出版年: | 2022 |
畢業學年度: | 110 |
語文別: | 中文 |
論文頁數: | 72 |
中文關鍵詞: | 白細胞介素-2 、環肽 、核磁共振 |
外文關鍵詞: | IL-2, cyclic peptide, nuclear magnetic resonance |
相關次數: | 點閱:3 下載:0 |
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白細胞介素-2 (Interleukin-2, IL-2) 於免疫反應中扮演重要角色,首次於研究中發現能作為T細胞生長因子,接著美國食品藥品監督管理局 (FDA) 亦批准其蛋白能用來治療黑色素瘤和腎細胞癌。然而,常見的問題為停留在體內的半衰期過短,在療程中需要施打高劑量的IL-2,導致了嚴重的副作用產生而限制其在治療上的效力。因此,設計出穩定的IL-2結構為我們研究的主要目的。
我們可以藉由排列蛋白質骨架序列來使其結構對於熱、酵素和化學物等外在刺激產生良好的結構抗性,我們將此原理運用在IL-2設計上,使目標蛋白形成穩定結構。研究過程中,我們成功得到兩個具活性的IL-2,並透過核磁共振儀 (NMR) 技術來觀察IL-2在不同條件下的水溶液結構,並與一般IL-2做比較。我們發現新型IL-2是成功的設計,具有相同的結構特性及極佳的活性,且在穩定度上有了大幅的提升,此結果幫助了我們在IL-2實驗設計上開拓了新的想法。
Interleukin-2 (IL-2) plays an important role in immune response. It was first discovered as a growth factor for T cells. The U.S. Food and Drug Administration (FDA) approved IL-2 in the clinical treatment of melanoma and renal cell carcinoma. However, the encountered problem is its short half-life in the body. The treatment need be compromised by injecting high doses of IL-2 that causes severe side effects and limits its therapeutic efficacy. Therefore, we intend to design a stable IL-2 in the study.
We can rearrange the protein backbone sequence to increase the structural resistance to external stimuli such as heat, enzyme and chemicals. We applied this concept in our research. Method of protein ligation was used to design the new IL-2. Here, we successfully prepared two stable IL-2s containing bioactivity. We employed NMR technology to observe the IL-2s and compare with native IL-2 in solution. Based on the structural similarity and substantial bioactivity, we conclude the method as a very successful strategy for improving IL-2 stability. This result gives us new direction for future IL-2 experimental and clinical application.
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