| 研究生: |
蘇靖舫 Su, Ching-Fang |
|---|---|
| 論文名稱: |
以多巴胺及穀胱甘肽修飾線性及星狀聚穀胺酸之抗氧化活性探討 Antioxidant Activity of Linear and Star-shaped Poly(L-glutamic acid) Polypeptides Modified with Dopamine and Glutathione |
| 指導教授: |
詹正雄
Jan, Jeng-Shiung |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 化學工程學系 Department of Chemical Engineering |
| 論文出版年: | 2020 |
| 畢業學年度: | 108 |
| 語文別: | 中文 |
| 論文頁數: | 98 |
| 中文關鍵詞: | 多巴胺 、穀胱甘肽 、穀胺酸 、星狀聚合物 、抗氧化 |
| 外文關鍵詞: | dopamine, glutathione, glutamic acid, star polymer, antioxidant |
| 相關次數: | 點閱:89 下載:1 |
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本研究利用一級胺及多元醇作為起始劑,以α-胺基酸 N-羧酸酐開環聚合法成功合成出線性與星狀聚榖胺酸,並利用EDC/NHS法將多巴胺及穀胱甘肽接枝於聚穀胺酸上,製備出一系列具抗氧化活性的接枝聚合物,再以1H NMR、MALDI-TOF、GPC及UV-vis光譜鑑定其聚合度、分子量及接枝量,探討不同分子型態及抗氧化劑種類對接枝聚合物的抗氧化活性影響。透過三種抗氧化活性測定,皆可發現純聚穀胺酸 (PLG) 幾乎沒有抗氧化活性;聚穀胺酸-接枝-穀胱甘肽 (PLG-GSH) 之抗氧化能力相較於純穀胱甘肽明顯減弱許多;聚穀胺酸-接枝-多巴胺 (PLG-Dopa) 與聚穀胺酸-接枝-多巴胺/穀胱甘肽 (PLG-Dopa-GSH) 之抗氧化能力則隨著高分子濃度上升而增強,可知其抗氧化活性主要是由多巴胺賦予,且抗氧化活性EC50隨著臂數增加而降低,與高分子多臂造成的立體結構效應有關,將抗氧化劑小分子接枝於聚胺基酸側鏈後,星狀接枝物能形成高抗氧化局部濃度之聚合物。最後透過溶血性及細胞活性測試確認接枝聚合物具備生物相容性與低細胞毒性,並比較抗氧化活性EC50與細胞存活率IC50,可發現PLG-Dopa-GSH之EC50皆小於其IC50,表示在較低高分子濃度下即可達到抑制生物體內50%的自由基而不會造成細胞毒性,其中又以6-armed PLG-Dopa-GSH效能最佳,可知星狀聚穀胺酸能透過接枝方法形成一高抗氧化活性、低細胞毒性之抗氧化劑,極具發展性。
The aim of this study was to investigate the effects of topology and antioxidants on the antioxidant-grafted polypeptides. The linear and star-shaped poly(L-glutamic acid) (PLG) polypeptides were synthesized by N-carboxyanhydrides (NCAs) ring opening polymerization (ROP) using primary amine and polyols as initiators, followed by deprotection. Graft copolypeptides (PLG-Dopa, PLG-GSH and PLG-Dopa-GSH) were obtained by EDC/NHS coupling chemistry using dopamine (Dopa) and glutathione (GSH). Successful synthesis of these polypeptides was confirmed by 1H NMR, MALDI TOF, GPC, UV-vis and IR spectra analyses. The conformation of polypeptides was investigated by circular dichroism (CD) spectroscopy, demonstrating the grafting of Dopa and GSH onto PLG was accompanied by a conformational change from a random coil to α–helical structure. The results showed that the antioxidant activities of PLG-Dopa and PLG-Dopa-GSH were ascribed to Dopa instead of GSH. Our experimental data showed that multi-armed polypeptides exhibited better antioxidant activity than linear ones, which could be attributed that they could form a dense structure with higher local antioxidant concentration. It was found that both PLG-Dopa and PLG-Dopa-GSH exhibited low hemolysis, suggesting good hemocompatibility. These graft copolypeptides with a given concentration to inhibit 50% free radicals would not cause cytotoxicity.
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