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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 王勝仕 | |
dc.contributor.author | Jun-Kun Lai | en |
dc.contributor.author | 賴潤錕 | zh_TW |
dc.date.accessioned | 2021-06-15T04:57:35Z | - |
dc.date.available | 2015-07-30 | |
dc.date.copyright | 2010-07-30 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-07-29 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46196 | - |
dc.description.abstract | 蛋白質是生物體內重要的組成元素,在各種生理活動扮演著不可或缺的角色。酵素是一種以蛋白質為構造主體的催化劑,用以促進生物體內各種特定生化反應之進行。具有正確構形的蛋白質,才能發揮其本身的功能,進行各種反應,酵素亦是如此,而摺疊錯誤的蛋白質不僅可能失去其正常之功能,更可進而產生聚集體,導致疾病的發生。
本論文中,吾人嘗試對於多胜肽和蛋白質分子間之作用進行探討,藉由不同組成、比例之共聚多胜肽對蛋白質進行包覆、吸附等方式,進而維持蛋白質構形。此外,並利用共聚多胜肽試驗其對於蛋白質折疊、結構變化和聚集、類澱粉纖維生成之影響。 本論文第一部份,以木瓜酵素為模型酵素,藉由嵌段共聚多胜肽Lys-b-Gly形成囊泡(vesicle)後,再結合與矽之礦化作用(mineralization)形成矽網絡結構完成固定化。相對於未固定化和只由囊泡包覆之酵素,本系統polypeptide mediated silica-immobilized papain提升木瓜酵素對於pH值變化和熱之穩定性以及重覆使用率(例如在25°C下放置48小時後,以0小時的活性為基準,固定化之系統保持約68.5%的活性、未固定化之組別約29.6%之活性)。藉由多胜肽所形成之矽網絡結構保護木瓜酵素,進而維持固定化酵素之活性。由動力學分析得知,矽/多胜肽形成網絡結構之特性和構形,對於酵素之功能有著重要的影響。 本論文第二部份,以牛胰島素和母雞蛋白溶菌酶為模型,探討兩種隨機共聚多胜肽D,L-lysine-co-glycine和D,L-lysine-co-L-phenylalanine對於在試管內之蛋白質形成類澱粉纖維的影響。由穿透式電子顯微和ThT螢光光譜分析之實驗結果觀察得知,對於抑制類澱粉纖維生成之效果,主要受到所加入多胜肽之數量和組成比例的影響。例如在添加1 mM隨機共聚多胜的組別中,母雞蛋白類澱粉纖維的形成受到約35 %的抑制,而添加2 mM之組別,則可達到約65 %之抑制效果。而對於牛胰島素,加入0.5mM或是1mM隨機共聚多胜則可達到約25 %或是80 %之抑制效果。隨著共聚多胜肽中glycine 或是phenylalanine之比例提高,對於抑制類澱粉纖維生成有更好的效果。此外,吾人藉由圓二色光譜、ANS 螢光光譜、自身螢光光譜和SDS-PAGE等分析方法探討兩種蛋白質的結構變化以及抑制機制。母雞蛋白溶菌酶和共聚多胜肽間的作用力由實驗結果推測主要可能為氫建和疏水作用力。由研究結果,有助於了解類澱粉纖維生成的過程中,蛋白質分子結構變化及詳細機制,並可更進一步對治療類澱粉症提供有效的策略。 | zh_TW |
dc.description.abstract | Proteins are essential elements for living organisms and play a crucial role in various physiological activities. An enzyme is a protein molecule that serves as a biological catalyst. Proteins/enzymes with correct conformations are able to serve appropriate biological functions. Proteins that misfold may not only lose their normal biological function but also form aggregates which lead to a variety of diseases.
In this thesis, we attempt to explore the interactions between the polypeptides and protein molecules. The preservation of protein conformation was carried out by copolypeptides with different compositions through various processes such as entrapment, or adsorption. Moreover, we examined the effects of polypeptides on folding, structural changes, aggregation, and amyloid fibrillation of proteins. In the first part of the thesis, we report the immobilization of a model enzyme, papain, within silica matrices by combining vesiclization of poly-L-lysine-b-polyglycine block copolypeptides with following silica mineralization. The polypeptide mediated silica-immobilized enzyme exhibits enhanced pH and thermal stability and reusability, comparing with the free enzyme and the vesicle encapsulated enzyme (e.g. after 48 hr incubation at 25°C, the percentage residual activities for the immobilized and the untreated papain samples were found to be ~68.5% and ~29.6% of that of the free papain at 0 hr, respectively). The enhanced enzymatic activity in the immobilized enzyme is due to the confinement of the enzyme in the polypeptide mediated silica matrices. Kinetic analysis shows that the enzyme functionality is determined by the structure and property of silica/polypeptide matrices. In the second part of the thesis, with hen egg-white lysozyme and bovine insulin as the model systems, we show the results regarding the influences of two random copolypeptide D,L-lysine-co-glycine and D,L-lysine-co-L-phenylalanine on the in vitro protein fibrillation. Our TEM and ThT fluorescence results show that the observed inhibitory effects on amyloid fibrillation are significantly dependent on the amount and the composition ratio of polypeptide chains. For instance, the percentage reduction in hen lysozyme fibrillation was found to be approximately 35 % or 65% for the case of 1 mM or 2 mM random copolypeptide, respectively. The addition of 0.5 mM or 1 mM random copolypeptide results in approximately 25 % or 80% reduction, respectively, in fibrillogenesis derived from bovine insulin. The copolypeptides with a higher fraction of glycine or L-phenylalanine residue exhibit higher inhibitory potency against fibril formation. Moreover, we examine the structural changes in both proteins and inhibition mechanisms through CD spectroscopy, ANS fluorescence, intrinsic fluorescence spectroscopy, and SDS-PAGE. The major driving forces for the association of HEWL and copolypeptides are likely hydrogen bonding and hydrophobic interactions. We believe that the outcome of this work may contribute to the understanding of molecular mechanism(s) of the fibril formation and provide potential treatment strategies against the amyloid formation associated with amyloid disease. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T04:57:35Z (GMT). No. of bitstreams: 1 ntu-99-R97524005-1.pdf: 5261632 bytes, checksum: 8ef0d8b51d4609dfe1247dde85211698 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 摘要 I
Abstract III 目錄 V 圖目錄 VIII 表目錄 XIII 第一章 緒論 1 第二章 文獻回顧 3 2-1 蛋白質簡介 3 2-2 蛋白質的結構 6 2-3 穩定蛋白質構造之作用力 12 2-4 蛋白質的構形(conformatiom) 15 2-5 蛋白質的摺疊 17 2-6 酵素簡介 19 2-7 蛋白質變性和酵素失活之因素 21 2-8 木瓜酵素(papain)之介紹 24 2-9 溶菌酶(lysozyme) 之簡介 30 2-9-1 母雞蛋白溶菌酶之結構 31 2-10 胰島素(insulin)之簡介 34 2-10-1 牛胰島素之結構 35 2-11固定化之簡介 38 2-12奈米粒子與多胜肽之簡介 41 2-13聚集體 48 2-13-1 聚集體的生成 49 2-13-2 類澱粉症 51 2-14 蛋白質構形變化與聚集之偵測方法簡介 52 2-14-1 Thioflavin T (ThT) 螢光光譜方法 52 2-14-2 ANS 螢光光譜方法 53 2-14-3 Congo red鍵結方法 54 2-14-4 圓二色光譜方法 56 2-14-5 蛋白質電泳方法(protein electrophoresis) 58 2-14-6 自身螢光光譜(Intrinsic fluorescence spectroscopy) 58 2-14-7 穿透式電子顯微鏡 59 2-14-8 蛋白質濃度測定 59 第三章 研究動機 61 第四章 實驗儀器、藥品與步驟 63 4-1 實驗裝置 63 4-2 實驗藥品 64 4-3 實驗方法和步驟 66 4-3-1 嵌段共聚多胜肽 66 4-3-1-1 多胜肽利用包覆方式固定化木瓜酵素 66 4-3-1-2 多胜肽和矽利用包覆方式固定化木瓜酵素 67 4-3-1-3 木瓜酵素濃度測定 67 4-3-1-4 木瓜酵素活性測定 68 4-3-1-5 實驗條件和動力學測定 68 4-3-1-6 遠紫外光圓二色光譜分析 (Far-UV circular dichroism spectrometry) 69 4-3-1-7 穿透式電子顯微鏡 (transmission electron microscopy, TEM) 69 4-3-2 隨機共聚多胜肽 69 4-3-2-1 隨機共聚多胜肽濃度對牛胰島素類澱粉纖維形成之影響 69 4-3-2-2 隨機共聚多胜肽對母雞蛋白類澱粉纖維形成之影響 70 4-3-2-3 ThT螢光光譜分析 (Thioflavin T fluorescence spectroscopy) 70 4-3-2-4 ANS螢光光譜分析 (ANS fluorescence spectroscopy) 70 4-3-2-5 Congo red鍵結分析 (Congo red binding assay) 71 4-3-2-6 遠紫外光圓二色光譜分析 (Far-UV circular dichroism spectrometry) 71 4-3-2-7 SDS-蛋白質電泳 (SDS-PAGE) 72 4-3-2-8 穿透式電子顯微鏡 (transmission electron microscopy, TEM) 74 4-3-2-9自身螢光光譜分析 (intrinsic fluorescence spectroscopy) 74 4-3-2-10蛋白質之濁度測定(turbidity measurement) 74 第五章 結果與討論 75 5-1 嵌段共聚多胜肽對木瓜酵素結構和活性之影響 75 5-1-1 嵌段共聚多胜肽固定化包覆效率之分析 76 5-1-2 固定化後之結構組成分析 78 5-1-3 嵌段共聚多胜肽固定化之熱穩定性分析 80 5-1-4 嵌段共聚多胜肽固定化對於pH值穩定性分析 83 5-1-5 遠紫外光圓二色光譜分析 85 5-1-6 酵素動力學之分析 88 5-1-7 固定化之重複使用性 90 5-2 隨機共聚多胜肽對母雞蛋白類澱粉纖維形成之影響 91 5-2-1 ThT螢光光譜分析 92 5-2-2 ANS螢光光譜分析 95 5-2-4 遠紫外光圓二色光譜分析 99 5-2-5 自身螢光光譜分析 106 5-2-6 穿透式電子顯微鏡分析 108 5-2-7 濁度和SDS蛋白質電泳分析 110 5-2-8 隨機共聚多胜肽對母雞蛋白類澱粉纖維生成之影響討論 114 5-3 隨機共聚多胜肽對牛胰島素類澱粉纖維形成之影響 115 5-3-1 ThT螢光光譜分析 116 5-3-2 ANS螢光光譜分析 118 5-3-3 Congo red鍵結測試 120 5-3-4 遠紫外光圓二色光譜分析 122 5-3-5 自身螢光光譜分析 129 5-3-6 穿透式電子顯微鏡分析 131 5-3-7 濁度和SDS蛋白質電泳分析 133 5-3-8 隨機共聚多胜肽對牛胰島素類澱粉纖維生成之影響討論 137 第六章 結果討論與建議 138 6-1 嵌段共聚多胜肽對於穩定木瓜酵素結構與活性之影響 138 6-2 隨機共聚多胜肽對於類澱粉纖維與蛋白質結構之影響 139 6-2-1 牛胰島素和母雞蛋白溶菌酶形成類澱粉纖維之機制 141 6-2-2 隨機共聚多胜肽濃度提升抑制牛胰島素和母雞蛋白溶菌酶形成類澱粉纖維之機制 141 6-3隨機共聚多胜肽對於牛胰島素和母雞蛋白溶菌酶延遲期之影響 142 6-4隨機共聚多胜肽對於牛胰島素和母雞蛋白溶菌酶作用力之探討 143 6-5建議與未來展望 145 參考文獻 146 附錄A 合成共聚多胜肽 157 A-1 乾燥溶劑 157 A-2 合成起始劑 157 A-3 製備α-胺基酸的N-carboxyanhydrides(NCAs) 157 A-4 胺基酸聚合反應 158 A-5 切除多胜肽之保護基 159 附錄B 牛胰島素和母雞蛋白類澱粉纖維成長動力學 160 | |
dc.language.iso | zh-TW | |
dc.title | 探討多胜肽與蛋白質分子間之交互作用 | zh_TW |
dc.title | Intercations between Polypeptide and Protein molecules | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 劉懷勝,林達顯,侯劭毅,詹正雄 | |
dc.subject.keyword | 溶菌酶,胰島素,木瓜酵素,類,澱粉纖維,共聚多胜肽,抑制,囊泡, | zh_TW |
dc.subject.keyword | lysozyme,amyloid fibril,insulin,papain,copolypeptide,inhibition,vesicle, | en |
dc.relation.page | 165 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2010-07-29 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 化學工程學研究所 | zh_TW |
顯示於系所單位: | 化學工程學系 |
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