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姓名	謝沁芸(Chin-Yun Hsieh)  查詢紙本館藏	畢業系所	化學學系
論文名稱	研究化學修飾的胜肽水凝膠 (The study of chemically-engineered peptide hydrogel)
檔案	[Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   至系統瀏覽論文 (2027-12-31以後開放)
摘要(中)	自組裝 (Self-assembly) 是由無序分子透過特定、局部交互作用組織成具功能性且有序結構的自發性聚集過程，也是常見製成奈米結構的方式。自組裝在科學上受到大量關注的原因之一為其對於生命體的重要性，如形成生物體最小的組成單位細胞，是由自組裝的磷脂質、蛋白質、DNA 四聯體以及其他分子所組成。自組裝材料中有一類具水溶性官能基的分子，能構成奈米等級的三維交聯網狀結構，在含水的環境下，水分子會被吸附在此網狀結構中，形成巨觀下的水凝膠 (Hydrogel) 。一般常見水凝膠原料分為合成及天然兩種：合成原料的水凝膠，如聚乙烯醇、聚丙烯酸等，通常分子容易修飾、混摻且擁有不錯的機械性質。天然原料的水凝膠，如玻尿酸、明膠、胜肽等，通常具有高度的生物相容性以及生物降解性。其中，氨基酸所構成 的胜肽水凝膠同時具有合成及天然原料的優點。因其分子小，能透過改變氨基酸組成或化學修飾，以調整水凝膠的機械性質或成膠條件。本篇研究以化學合成的方式，合成一系列化學修飾的胜肽。在穿透式電子顯微鏡中，我們觀察到此類胜肽在酸性與中性下為球狀，在鹼性下則為纖維狀 (巨觀下為水凝膠) 的結構，說明 pH 值可調控胺基酸帶電的比例，進而影響到自組裝結構。而後，我們嘗試改變胜肽濃度、胜肽親疏水性對成膠的影響，發現高胜肽濃度及高疏水性胺基酸可促使化學修飾胜肽在較低的pH值下成膠。根據實驗結果以及文獻參考，當胜肽序列引入更為疏水的氨基酸後可於中性環境成膠。最後，我們也將老鼠纖維母細胞 (L929 mouse fibroblast) 培養在水凝膠上，成功驗證此人工合成胜肽為生物相容性的材料。
摘要(英)	Self-assembly is the spontaneous aggregation process which disordered molecules organize into ordered or functional structures through specific interactions, which is a common way of building nanostructures. In life science, self-assembly processes are widely identified in cell biology, including the formations of phospholipid membrane, protein superstructure, DNA quadruplex and other molecules. Among them, some amphiphilic materials form three-dimensional interconnected network structure. This network structure in an aqueous environment will absorb water to form hydrogel at the macroscopic level. Common hydrogel-forming materials can be divided into two categories including synthetic materials [e.g., poly(acrylic acid) and polyethylene glycol] and natural ones (e.g., hyaluronic acid and peptide). Synthetic materials have strong mechanical properties and easy to modify through the change of monomers. On the other hand, natural materials benefit from their superior biocompatibility and biodegradability. Among these cases, peptide-based hydrogel possesses the advantage of both cases. They are biocompatible and easy to modify through the change of sequence or amino acid modification. In this study, we designed a series of chemically-engineer peptides for preparing hydrogel. We observed that some peptides self-assembled into spherical-like structures in acid or neutral conditions but transformed into hydrogel with nano-fibrils in base conditions. We also found that high peptide concentration and the addition of hydrophobic amino acids could promote gel formation. Moreover, increasing the hydrophobicity makes the peptide able to form hydrogel in neutral condition. Finally, we successfully seeded L929 fibroblast cells onto the hydrogel at neutral pH value, indicating this chemically-engineered peptides could be applied as a biocompatible material.
關鍵字(中)	★ 胜肽水凝膠	關鍵字(英)
論文目次	摘要 i Abstract ii 致謝 iii 目錄 iv 圖目錄 vi 表目錄 ix 附錄目錄 x 第一章 緒論 1 1-1 分子自組裝 1 1-2 常見的自組裝材料及結構之應用 2 1-3 水凝膠 (Hydrogel) 性質和應用 4 1-4 胜肽水凝膠 (Peptide-based hydrogel) 6 1-5 研究動機與目的 7 第二章 實驗儀器及藥品 9 2-1 實驗儀器 9 2-2 實驗藥品 10 2-2-1 胜肽合成藥品與純化試劑配置 10 2-2-2 實驗藥品 11 第三章 實驗方法 13 3-1 樣品製備 13 3-1-1 固相胜肽合成方法 (Solid Phase Peptide Synthesis, SPPS) 13 3-1-2 高效液相層析 (High-Performance Liquid Chromatography) 16 3-1-3 基質輔助雷射脫附游離化法 (MALDI Mass Spectroscopy) 17 3-2 自組裝胜肽材料性質分析 19 3-2-1 穿透式電子顯微鏡 (Transmission Electron Microscopy, TEM) 19 3-2-1-1 胜肽樣品負染步驟 20 3-2-2 流變儀 (Rheometer) 21 3-2-3 界面電位分析 (Zeta potential analysis) 22 3-3 三維水凝膠細胞培養 23 3-3-1 水凝膠製備與細胞培養 23 3-3-2 螢光染色 24 第四章 實驗結果 25 4-1 自組裝胜肽水凝膠劑之設計 25 4-2 自組裝胜肽合成、純化與鑑定 27 4-3 胜肽自組裝性質鑑定 28 4-4 pH值對胜肽自組裝之影響 29 4-4-1 Lys+去質子化對胜肽自組裝之影響 31 4-4-2 纖維狀、球形結構示意圖 33 4-5 胜肽濃度對胜肽自組裝之影響 35 4-6 pH值、胜肽濃度對自組裝胜肽之成膠影響 37 4-7 胜肽親疏水性序列調控對胜肽自組裝之影響 39 4-7-1 胜肽親疏水性序列調控對自組裝胜肽之成膠影響 42 4-8 芳香環平面性修飾對自組裝胜肽之成膠影響 47 4-9 未修飾芘羧酸胜肽自組裝之影響 49 4-10 Pyr-L3K3水凝膠性質鑑定 50 4-10-1 水凝膠之黏彈性 50 4-10-2 水凝膠之界面電位 51 4-10-3 水凝膠之親疏水性 52 4-10-4 三維水凝膠細胞培養 53 第五章 實驗討論 55 第六章 總結 57 附錄 58 參考文獻 64
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指導教授	黃人則 謝發坤(Jen-Tse Huang Fa-Kuen Shieh)	審核日期	2022-7-26
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