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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 王勝仕(Sheng-Shih Wang) | |
dc.contributor.author | Tzu-Horng Wang | en |
dc.contributor.author | 王梓鴻 | zh_TW |
dc.date.accessioned | 2021-06-07T17:40:36Z | - |
dc.date.copyright | 2020-08-11 | |
dc.date.issued | 2020 | |
dc.date.submitted | 2020-08-06 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/15435 | - |
dc.description.abstract | 類澱粉纖維疾病是因為蛋白質形成的類澱粉纖維堆積在人體所造成,並讓身體器官或組織無法發揮正常功用,但在部分特定物質存在的環境下,像是多酚類,金屬奈米粒子,滲透物質,可以減緩類澱粉纖維的生成。吾人使用在酸性環境下加熱核糖跟半乳糖溶液所形成的糖類奈米粒子作為蛋白質類澱粉纖維化的抑制劑,以及使用母雞白蛋白溶菌酶作為研究目標,因為其結構與人類溶菌酶蛋白相近,並藉由不同分析方法,檢驗糖奈米粒子如何影響Lysozyme類澱粉纖維化。 藉由ThT螢光分析跟電子顯微鏡觀察發現,醣類奈米粒子在抑制Lysozyme類澱粉纖維化上均有明顯效果。從ANS螢光分析結果發現,Lysozyme裸露的疏水區域會隨著核糖和半乳糖兩種糖類奈米粒子添加量的上升而減少。此外,從圓二色光譜分析結果也發現添加兩種糖類奈米粒子到Lysozyme中,蛋白質的β-sheet結構比例上升幅度會降低。藉由螢光淬滅實驗並改變溫度條件可以推估蛋白質跟糖奈米粒子間作用的熱力學參數。首先,實驗結果顯示出兩種物質相互混合的過程是吸熱反應,並且使整個系統的亂度增加,因此推測奈米粒子和蛋白質之間結合的交互作用力是以疏水作用力為主。再者,發現在不同溫度下,核糖奈米粒子跟Lysozyme之間的結合常數跟結合位點數都大於半乳糖奈米粒子的,推測Lysozyme跟核糖奈米粒子之間的親和力較高。此外,從光散射跟電泳實驗結果分別得知添加糖奈米粒子能降低蛋白質形成較大的聚集,並使Lysozyme維持原態單體結構。 綜上所述,不管是添加核糖或是半乳糖奈米粒子跟其分子形式相比能更有效抑制Lysozyme類澱粉纖維的出現,儘管Lysozyme並不被認為是常見類澱粉纖維症的致病蛋白,但藉由了解糖奈米粒子對Lysozyme類澱粉纖維形成之影響,希望能對於未來開發奈米尺寸抑制劑的研究發展做出貢獻。 | zh_TW |
dc.description.abstract | Amyloidosis is caused by the acccumulation of protein amyloid fibrils in human body, which results in the malfunction of tissues and organs. But in the presence of some certain materials, such as polyphenol, metal nanoparticles, and osmolytes, the process of protein fibrillation would be retarded. By heating of ribose and galactose solution in acid condition, we could synthesize the ribose and galactose-based nanoparticles as inhibitor of amyloid fibril formation. We used hen egg white lysozyme as our reseach target because it is structurly similar to human lysozyme. By differenet kinds of analytical methods, we could examine how the sugar-based nanoparticles affected lysozyme fibrillation. Via ThT fluorescence assay and transmission electron microscopy, we found that the sugar-based nanoparticles could reduce hen egg white lysozyme fibrillation effectively. From the ANS fluorescence experiment results, we concluded that the more ribose-based and galactose-based nanoparticles we added into the lysozyme solution, the less hydrophobic area of hen egg white lysozyme was exposed to external environment. Furthermore, the CD spectroscopy results showed that the β-sheet structure of hen egg white lysozyme grew slowly in the presence of the sugar-based nanoparticles. In addition, by conducting fluorescence quenching experiment at different temperatures, we could derive the thermodynamic parameters of the interaction between hen egg white lysozyme and the nanoparticles. Firstly, the mixing process of proteins and the nanoparticles was endothermic, and the entropy change of the system was greater than zero, implying that the combination of sugar-based nanopaticles and proteins was mainly caused by hydrophobic force. Secondly, in comparison of galactose-based nanoparticle, the binding constants and the binding sites between ribose-based nanoparticle and hen egg white lysozyme at three different temperatures were large, which indicated that hen egg white lysozyme has much more affinity toward the ribose-based nanoparticle. Moreover, as revealed by the right-angle light scattering experiment and electrophoresis results, the protein aggregates size decreased and the hen egg white lysozyme maintained its native monomer structure while incubated with the nanoparticles. In summary, our study proved that the sugar-based nanoparticles possessed better inhibition efficiency than their molecular form. Despite the fact that lysozyme is not considered to be a common pathological protein, we hope that realizing the influence of the sugar-based nanoparticles on hen egg white lysozyme fibrillation could contribute to the development of nano-sized inhibitors in other research. | en |
dc.description.provenance | Made available in DSpace on 2021-06-07T17:40:36Z (GMT). No. of bitstreams: 1 U0001-2307202013174700.pdf: 4567824 bytes, checksum: e86ffece2aefed405631697356383e0f (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | 誌謝 I 摘要 II Abstract IV 目錄 VI 圖目錄 IX 表目錄 XIV 第一章 緒論與研究動機 1 第二章 文獻回顧 2 2-1 蛋白質 2 2-1-1 胺基酸 2 2-1-2 蛋白質各級結構 3 2-1-3 蛋白質變性(Protein Denaturation) 4 2-2 類澱粉纖維 5 2-3 母雞白蛋白溶菌酶(hen egg white lysozyme, HEWL) 6 2-3-1 溶菌酶形成的類澱粉纖維 7 2-4 奈米粒子 8 2-4-1 奈米粒子-蛋白質冠冕形成 10 2-4-2 奈米粒子對蛋白質結構之影響 11 2-4-3 奈米粒子對蛋白質纖維化之影響 12 2-4-4 奈米粒子對血腦屏障(Blood Brain Barrier)之影響 19 2-5 滲透物Osmolyte 20 2-5-1 有機滲透物質類別 20 2-5-2 核糖Ribose 21 2-5-3 半乳糖Galactose 22 2-5-4 滲透物對蛋白質纖維化之影響 23 2-5-5 醣類滲透物所形成奈米粒子對類澱粉纖維生成之影響 31 2-6實驗原理介紹 32 2-6-1 蒽酮試劑測試(Anthrone Test) 32 2-6-2 Thioflavin T螢光光譜 32 2-6-3ANS螢光光譜 34 2-6-4 圓二色(Circular Dichroism)光譜 34 2-6-5 自身螢光光譜(Intrinsic Fluorescence Spectroscopy) 35 2-6-6 螢光淬滅(Fluorescence Quenching) 36 2-6-7 SDS-PAGE蛋白質電泳 38 第三章 實驗儀器、藥品與步驟 40 3-1實驗儀器 40 3-2實驗藥品 41 3-3實驗方法及步驟 43 3-3-1製備核糖跟半乳糖奈米粒子(sugar-based nanoparticle) 43 3-3-2蒽酮試劑檢測表面糖基濃度 44 3-3-3 糖奈米粒子Ultraviolet-visible light (UV-vis) 44 3-3-4 糖奈米粒子Transmission electron microscopy (TEM) 45 3-3-5糖奈米粒子動態光散射(DLS) 45 3-3-6 Buffer、螢光染劑、蛋白質溶液製備 46 3-3-7製備Lysozyme類澱粉纖維樣品及相關實驗 47 第四章 實驗結果與討論 52 4-1 核糖與半乳糖奈米粒子性質檢定 52 4-1-1核糖與半乳糖奈米粒子表面糖基濃度 52 4-1-2糖奈米粒子UV-vis吸收及螢光放射光譜 54 4-1-3穿透式電子顯微鏡(TEM)分析 55 4-1-4動態光散射粒徑分析 56 4-2 糖奈米粒子對Lysozyme纖維化跟結構影響結果 58 4-2-1 Thioflavin T 螢光光譜 58 4-2-2 ANS螢光光譜 63 4-2-3 圓二色光譜 67 4-2-4 穿透式電子顯微鏡 71 4-2-5 自身螢光光譜 74 4-2-6 螢光淬滅 77 4-2-7 Right-angle Light Scattering 84 4-2-8 SDS-PAGE 蛋白質凝膠電泳 85 第五章 結論 88 附錄 90 附錄A核塘跟半乳糖奈米粒子對螢光實驗之影響 90 附錄B糖奈米粒子蔥酮試驗吸收光譜圖 92 附錄C核糖及半乳糖奈米粒子對Lysozyme類澱粉纖維化抑制之動力學模型 93 參考文獻 95 | |
dc.language.iso | zh-TW | |
dc.title | 探討核糖跟半乳糖奈米粒子於抑制母雞溶菌酶蛋白類澱粉纖維形成之影響 | zh_TW |
dc.title | Examining the Effects of Ribose-based and Galactose-based Nanoparticles on Amyloid Fibril Formation of Hen Lysozyme | en |
dc.type | Thesis | |
dc.date.schoolyear | 108-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林達顯(Ta-Hsien Lin),侯劭毅(Shao-Yi Hou),蔡伸隆(Shen-Long Tsai),賴進此(Jin-Cih Lai),吳宛儒(Wan-Ru Wu) | |
dc.subject.keyword | 類澱粉纖維,奈米粒子,核醣,半乳糖,抑制劑,母雞白蛋白溶菌酶, | zh_TW |
dc.subject.keyword | amyloid fibrils,nanoparticle,ribose,galactose,inhibitor,hen egg white lysozyme, | en |
dc.relation.page | 101 | |
dc.identifier.doi | 10.6342/NTU202001775 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2020-08-07 | |
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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