請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/21573完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 王勝仕(Sheng-Shin Wang) | |
| dc.contributor.author | Jian-Hong Lu | en |
| dc.contributor.author | 呂建宏 | zh_TW |
| dc.date.accessioned | 2021-06-08T03:38:23Z | - |
| dc.date.copyright | 2019-07-19 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-07-17 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/21573 | - |
| dc.description.abstract | 白內障是全世界視力受損的主要原因之一，為一種眼睛水晶體內之蛋白質聚集相關的疾病，一些風險因素包含紫外光照射會誘導水晶體蛋白去折疊以及隨後的水晶體蛋白聚集，而造成水晶體混濁。人類水晶體核心中富含許多水晶體蛋白，其主要功能為協助維持水晶體的光學性質，然而長時間曝曬於太陽光底下，其紫外光照射會致使水晶體蛋白產生聚集體，導致引發老年性白內障。此外有證據顯示於酸性條件下有類澱粉纖維物種的形成，而被認為是老年型白內障發展過程的路徑之一。
本論文旨在探討幾種潛在的小分子物質對於人類γD型水晶體蛋白(HγDC)聚集與其類澱粉纖維形成之影響，於論文的第一部分，ortho-vanillin、myricetin與rosmarinic acid等小分子物質用於測試並探討由UV-C誘導聚集的抑制效果，使用turbidity、right angle light scattering、SDS-PAGE、TEM、遠紫外光圓二色光譜、ANS螢光光譜以及分子對接模擬等分析，研究結果發現HγDC與小分子物質莫耳比1:10情況下，ortho-vanillin、myricetin與rosmarinic acid於right angle light scattering結果顯示其光散射下降百分比分別為~76.85±2.48%, ~73.53±1.95%, ~12.85±4.60%，並與TEM和SDS-PAGE結果指出ortho-vanillin是三種檢測小分子物質中，對抗UV-C觸發之聚集為最有效的抑制劑，而分子對接模擬揭示出這些小分子物質和原態HγDC之間的結合中存在著氫鍵、靜電作用力和π-π共軛堆積等相互作用力。 第二部分研究chlorazol Black E、myricetin與5-hydroxy-1,4-naphthoquinone如何於酸性條件(pH=2)下影響HγDC之類澱粉纖維形成，使用ThT螢光光譜、tryptophan螢光光譜、ANS螢光光譜、SDS-PAGE、TEM、遠紫外光圓二色光譜與分子對接模擬等分析，發現於小分子物質300μM情況下，其抑制效果依序為: chlorazol Black E (ThT螢光下降百分比= ~82.47±4.03%) > myricetin (ThT螢光下降百分比= ~65.45±1.84%) > 5-hydroxy-1,4-naphthoquinone (ThT螢光下降百分比= ~57.91±3.61%)，使用分子對接模擬並了解到這些潛在的小分子物質，可能透過與HγDC之類澱粉纖維聚集熱點的結合，而干擾其類澱粉纖維之形成。 本研究成功地展示出某些小分子物質可用於抑制HγDC的無定型體聚集以及類澱粉纖維形成，相信這項研究結果有助於設計臨床策略和開發抗白內障的抑制化合物。 | zh_TW |
| dc.description.abstract | Cataract is one of the main causes of visual impairment in the world. It is the disease associated with protein aggregation in the eye lens. Several risk factors including the exposure to ultraviolet irradiation may induce unfolding of the lens proteins, followed by aggregation of the lens proteins, thus leading to the opacification of the crystalline lens. Crystallin proteins are abundant in the nucleus of the human eye lens. They mainly function to maintain the optical properties of the lens. However, exposure to the sun's ultraviolet radiation for a prolonged period of time will cause the crystallin proteins to form aggregates, leading to age-related cataract. In addition, evidence suggests that crystallin proteins are able to form amyloid fibrillar species under the acidic conditions. It is considered to be one of the paths of the development of age-related cataract.
This thesis was aimed at investigating the effects of several potential small molecules on the aggregation and/or fibrillogenesis of human γD-crystallin proteins (HγDC). In the first part of the thesis, the small molecules, such as ortho-vanillin, myricetin, and rosmarinic acid were tested to explore the inhibitory effects against UV-C-induced aggregation using several techniques including turbidity, right angle light scattering, SDS-PAGE, TEM, far-ultraviolet circular dichroism spectroscopy, ANS fluorescence spectroscopy and molecular docking simulation. Our results demonstrated that, when the molar ratio of HγDC to small molecule was at 1:10, the percentage reduction of light scattering was found to be ~76.85±2.48%, ~73.53±1.95%, ~12.85±4.60% for ortho-vanillin, myricetin, or rosmarinic acid, respectively. Results from right angle light scattering, TEM, and SDS-PAGE suggested that ortho-vanillin is the most potent UV-C triggered aggregation inhibitor among the three agents examined. Molecular docking studies also revealed that there were various kinds of interacting forces (e.g., hydrogen bonding, electrostatic interactions, and π-π stacking) involved in the binding between these small molecules and native HγDC. In the second part, we studied how chlorazol Black E, myricetin, and 5-hydroxy-1,4-naphthoquinone affected amyloid fibril formation of HγDC which was induced under the acidic conditions (e.g., pH 2.0) using the techniques including ThT fluorescence spectroscopy, tryptophan fluorescence spectroscopy, ANS fluorescence spectroscopy, SDS-PAGE, TEM, far-ultraviolet circular dichroism spectroscopy, and molecular docking simulation. It was observed that, when the concentration of small molecule was 300 μM, the inhibitory activity followed the order: chlorazol Black E (the percentage reduction of ThT fluorescence = ~82.47±4.03%) > myricetin (the percentage reduction of ThT fluorescence = ~65.45±1.84%) > 5-hydroxy-1,4-naphthoquinone (the percentage reduction of ThT fluorescence = ~57.91±3.61%). We also performed molecular docking studies and learned that these potential small molecules may interfere with amyloid fibrillogenesis of HγDC via binding with the fibril formation hot spots or amyloidogenic regions of HγDC. Overall, our study successfully demonstrated that amorphous aggregation and amyloid fibril formation of HγDC could be suppressed by certain small molecules. We believe the outcome from this work may, in part, help to design clinical strategies and develop inhibitory compounds against cataracts. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T03:38:23Z (GMT). No. of bitstreams: 1 ntu-108-R06524004-1.pdf: 11691800 bytes, checksum: 88ef7e491d872881dfaee2eb21c47909 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 目錄
誌謝 I 摘要 II Abstract IV 目錄 VI 圖目錄 X 表目錄 XV 第一章 緒論與研究目的 1 第二章 文獻回顧 3 2-1人類水晶體(Lens) 3 2-2水晶體蛋白(Crystallins) 6 2-2-1 α型水晶體蛋白 7 2-2-2 β、γ型水晶體蛋白 9 2-2-3 γD型水晶體蛋白 12 2-3 白內障(Cataract) 28 2-4 紫外光對於水晶體蛋白之影響 32 2-5 酸性環境對於水晶體蛋白之影響 41 2-6 小分子物質(small molecules) 48 2-6-1 Ortho-vanillin 49 2-6-2 Myricetin 50 2-6-3 Rosmarinic acid 51 2-6-4 Chlorazol Black E 51 2-6-5 5-hydroxy-1,4-naphthoquinone 52 第三章 實驗儀器、藥品與步驟 54 3-1 實驗儀器 54 3-2 實驗藥品 55 3-2-1 小分子物質 55 3-2-2 藥品 55 3-3 藥品配製 57 3-4 實驗步驟 59 3-4-1 HγDC表達及純化 59 3-4-1-1 蛋白質生產與親合性純化 59 3-4-1-2 蛋白質定性分析(SDS-PAGE) 61 3-4-1-3 蛋白質定量分析(BCA assay) 62 3-4-2 UV-C紫外線照射對HγDC生成聚集體 62 3-4-2-1 UV-C紫外線照射方式 62 3-4-2-2 濁度(turbidity)量測 62 3-4-2-3 right angle light scattering量測 63 3-4-2-4 聚丙烯醯胺膠體電泳(sodium dodecyl sulfate polyacrylamide gel electrophoresis, SDS-PAGE) 63 3-4-2-5 穿透式電子顯微鏡(Transmission Electron Microscopy, TEM)量測 64 3-4-2-6 圓二色(Circular Dichroism, CD)光譜量測 64 3-4-2-7 8-Anilino-1-naphthalenesulfonic acid(ANS)螢光光譜量測 64 3-4-2-8 HγDC與小分子對接模擬(CDOCKER) 65 3-4-3 酸性環境對HγDC生成類澱粉纖維 67 3-4-3-1 培養類澱粉纖維 67 3-4-3-2 Thioflavin T(ThT)螢光光譜量測 67 3-4-3-3 Tryptophan螢光光譜量 68 3-4-3-4 8-Anilino-1-naphthalenesulfonic acid(ANS)螢光光譜量測 68 3-4-3-5 聚丙烯醯胺膠體電泳(sodium dodecyl sulfate polyacrylamide gel electrophoresis, SDS-PAGE) 69 3-4-3-6 穿透式電子顯微鏡(Transmission Electron Microscopy, TEM)量測 69 3-4-3-7 圓二色(Circular Dichroism, CD)光譜量測 70 3-4-3-8 HγDC與小分子對接模擬(CDOCKER) 70 第四章 實驗結果與討論 71 4-1 UV-C照射對HγDC生成聚集體 71 4-1-1 UV-C照射下HγDC外觀 71 4-1-2 濁度(turbidity)與right angle light scattering分析HγDC聚集體之生成 75 4-1-2-1 小分子物質吸收度 75 4-1-2-2 Turbidity 77 4-1-2-3 Right angle light scattering 83 4-1-3 SDS-PAGE蛋白質電泳分析 87 4-1-4穿透式電子顯微鏡(TEM)分析 96 4-1-5遠紫外光圓二色(Far Ultraviolet Circular Dichroism)光譜分析 97 4-1-6 ANS螢光光譜分析 100 4-1-7 CDOCKER分子對接模擬 107 4-1-7-1 Native HγDC對接模擬 108 4-1-7-2 Partially unfolded HγDC對接模擬 121 4-2 酸性環境對HγDC生成類澱粉纖維 127 4-2-1 酸性環境培養下HγDC外觀 127 4-2-2 Thioflavin T(ThT)螢光光譜分析 128 4-2-3 Tryptophan螢光光譜分析 133 4-2-4 ANS螢光光譜分析 137 4-2-5 SDS-PAGE蛋白質電泳分析 144 4-2-6穿透式電子顯微鏡(TEM)分析 146 4-2-7遠紫外光圓二色(Far Ultraviolet Circular Dichroism)光譜分析 147 4-2-8 CDOCKER分子對接模擬 150 第五章 結論與未來展望 158 第六章 參考文獻 161 附錄 177 附錄一 HγDC定性分析(SDS-PAGE) 177 附錄二 UV-C光照前後之SDS-PAGE電泳(with β-Me)-小分子物質ortho-vanillin 178 附錄三 UV-C光照前後之SDS-PAGE電泳(with β-Me)-小分子物質myricetin 179 附錄四 UV-C光照前後之SDS-PAGE電泳(with β-Me)-小分子物質rosmarinic acid 180 附錄五 UV-C光照前之穿透式電子顯微鏡(TEM)圖: (a) control HGDC, 0hr (b) ortho-vanillin 1:10, 0hr (c) myricetin 1:10, 0hr (d) rosmarinic acid 1:10, 0hr 181 附錄六 酸性環境培養前之穿透式電子顯微鏡(TEM)圖: (a)control HGDC, 0hr (b) chlorazol Black E 300μM, 0hr (c) myricetin 300μM, 0hr (d) 5-hydroxy-1,4-naphthoquinone 300μM, 0hr 182 附錄七 小分子物質吸收度(a) chlorazol Black E 300μM (b) 5-hydroxy-1,4-naphthoquinone 300μM 183 附錄八 酸性培養前後之SDS-PAGE電泳(without β-Me)彩色版 184 附錄九 HγDC於pH 2.0環境下各殘基二級結構對時間之變化圖[173] 185 附錄十 質體pEHisHγDC [160] 186 圖目錄 Figure 2-1 人類眼球結構圖 3 Figure 2-2 人類水晶體結構圖 4 Figure 2-3 人類αB型水晶體蛋白結構圖(a)monomer [PDB code: 3L1G] (b)oligomer [PDB code: 2WJ7] (c)24mer [PDB code: 3J07] 8 Figure 2-4 人類β、γ型水晶體蛋白結構示意圖 (a)單個Greek key motif (b)人類γB、γS型水晶體蛋白示意圖 (c)人類βB2型水晶體蛋白(dimer)[48] 10 Figure 2-5 人類β、γ型水晶體蛋白結構圖 (a)人類γB型水晶體蛋白[PDB code: 2JDF] (b)人類βB2型水晶體蛋白(dimer) [PDB code: 1BD7] 11 Figure 2-6 人類γD型水晶體蛋白結構圖(a)人類γD型水晶體蛋白[PDB code: 1HK0] (b)結構示意圖(四個Greek key motifs) 12 Figure 2-7 人類γD型水晶體蛋白結構圖(a)人類γD型水晶體蛋白(top view)[PDB code: 1HK0] (b)結構示意圖(aromatic residues位置) 13 Figure 2-8 人類γD型水晶體蛋白結構圖(位於interface殘基) 14 Figure 2-9 人類γD型水晶體蛋白開展與聚集模型 16 Figure 2-10 人類γD型水晶體蛋白開展模型(馬蹄形:Greek key motifs 六角形:Greek key aromatic pairs) 17 Figure 2-11 白內障類型及水晶體結構 (a)水晶體結構及不同白內障類型 (b)核型白內障(nuclear cataracts) (c)皮質型白內障(cortical cataracts) (d)後囊下型白內障(posterior subcapsular cataracts) 28 Figure 2-12白內障類型示意圖 29 Figure 2-13 太陽輻射光譜之分類(ISO 21348) 32 Figure 2-14 紫外光產生氧化自由基機制圖 35 Figure 2-15 HγDC聚集機制示意圖 36 Figure 2-16 Trp-to-KN之蛋白質側鏈修飾 37 Figure 2-17 人類水晶體蛋白之類澱粉纖維結構所佔百分比[169] 42 Figure 3-1分子結構圖 (a) HγDC (b)ortho-vanillin (c)myricetin (d)rosmarinic acid 65 Figure 3-2 蛋白質之binding site 66 Figure 3-3 CDOCKER模擬結果 66 Figure 3-4 分子間作用力分析 67 Figure 4-1 UV-C光照前後樣品外觀:(a)未照射 (b)兩小時照射後，ortho-vanillin莫耳濃度由左至右分別為0、90.90、227.27、454.54μM 72 Figure 4-2 UV-C光照前後樣品外觀:(a)未照射 (b)兩小時照射後，myricetin莫耳濃度由左至右分別為0、90.90、227.27、454.54μM 73 Figure 4-3 UV-C光照前後樣品外觀:(a)未照射 (b)兩小時照射後，rosmarinic acid莫耳濃度由左至右分別為0、90.90、227.27、454.54μM 73 Figure 4-4 小分子物質ortho-vanillin(500μM)之吸收光譜 75 Figure 4-5 小分子物質myricetin(500μM)之吸收光譜 76 Figure 4-6 小分子物質rosmarinic acid(500μM)之吸收光譜 76 Figure 4-7 UV-C光照前後之濁度全光譜圖-小分子物質ortho-vanillin (a)未照射 (b)兩小時照射後 78 Figure 4-8 UV-C光照前後之濁度全光譜圖-小分子物質myricetin (a)未照射 (b)兩小時照射後 80 Figure 4-9 UV-C光照前後之濁度全光譜圖-小分子物質rosmarinic acid (a)未照射 (b)兩小時照射後 82 Figure 4-10 UV-C光照前後之right angle intensity-小分子物質ortho-vanillin 83 Figure 4-11 UV-C光照前後之right angle intensity-小分子物質myricetin 84 Figure 4-12 UV-C光照前後之right angle intensity-小分子物質rosmarinic acid 85 Figure 4-13 UV-C光照前後之SDS-PAGE電泳(without β-Me)- ortho-vanillin 87 Figure 4-14 UV-C光照前後之SDS-PAGE(without β-Me) - myricetin 89 Figure 4-15 UV-C光照前後之SDS-PAGE電泳(without β-Me) - rosmarinic acid 91 Figure 4-16 UV-C光照後之SDS-PAGE電泳-綜合比較 93 Figure 4-17 UV-C光照後之穿透式電子顯微鏡(TEM)圖: (a) control HGDC, 2hrs (b) ortho-vanillin 1:10, 2hrs (c) myricetin 1:10, 2hrs (d) rosmarinic acid 1:10, 2hrs 96 Figure 4-18 UV-C光照前後之HγDC遠紫外光圓二色光譜圖 97 Figure 4-19(a)(b) UV-C光照前後之HγDC二級結構比例 99 Figure 4-20 UV-C光照前後之ANS螢光檢測-小分子物質ortho-vanillin: (a)螢光全光譜 (b)平均放射波長(A.E.W.) (c)平均放射波長下強度 102 Figure 4-21 UV-C光照前後之ANS螢光檢測-小分子物質myricetin: (a)螢光全光譜 (b)平均放射波長(A.E.W.) (c)平均放射波長下強度 104 Figure 4-22 UV-C光照前後之ANS螢光檢測-小分子物質rosmarinic acid: (a)螢光全光譜 (b)平均放射波長(A.E.W.) (c)平均放射波長下強度 106 Figure 4-23 HγDC與小分子物質於Binding site I的對接圖 (a)Binding site I (b)ortho-vanillin (c)myricetin (d)rosmarinic acid 110 Figure 4-24 HγDC與小分子物質於Binding site I的分子間作用力 (a)ortho-vanillin (b)myricetin (c)rosmarinic acid 111 Figure 4-25 HγDC與ortho-vanillin於Binding site II的對接圖 112 Figure 4-26 HγDC與ortho-vanillin於Binding site II的分子間作用力 113 Figure 4-27 HγDC與小分子物質於Binding site III的對接圖(a)Binding site III (b)ortho-vanillin (c)myricetin (d)rosmarinic acid 114 Figure 4-28 HγDC與小分子物質於Binding site III的分子間作用力 (a)ortho-vanillin (b)myricetin (c)rosmarinic acid 115 Figure 4-29 HγDC與小分子物質於Binding site IV的對接圖(a)Binding site IV (b)ortho-vanillin (c)myricetin (d)rosmarinic acid 116 Figure 4-30 HγDC與小分子物質於Binding site IV的分子間作用力 (a)ortho-vanillin (b)myricetin (c)rosmarinic acid 117 Figure 4-31 HγDC與小分子物質於Binding site V的對接圖(a)Binding site V (b)ortho-vanillin (c)myricetin (d)rosmarinic acid 118 Figure 4-32 HγDC與小分子物質於Binding site V的分子間作用力 (a)ortho-vanillin (b)myricetin (c)rosmarinic acid 119 Figure 4-33 HγDC(quadruple KN mutant) 500K環境下500~1500ps之平均結構 122 Figure 4-34 HγDC(quadruple KN mutant)與小分子物質於W42KN的分子間作用力 (a)ortho-vanillin (b)myricetin (c)rosmarinic acid 123 Figure 4-35 HγDC(quadruple KN mutant)與小分子物質於W68KN的分子間作用力 (a)ortho-vanillin (b)myricetin (c)rosmarinic acid 124 Figure 4-36 HγDC(quadruple KN mutant)與小分子物質於W131KN的分子間作用力 (a)ortho-vanillin (b)myricetin (c)rosmarinic acid 125 Figure 4-37 HγDC(quadruple KN mutant)與小分子物質於W157KN的分子間作用力 (a)ortho-vanillin (b)myricetin (c)rosmarinic acid 126 Figure 4-38 酸性環境培養前樣品外觀:由左至右分別為control HγDC、chlorazol Black E 100μM、chlorazol Black E 300μM、5-hydroxy-1,4-naphthoquinone 100μM、5-hydroxy-1,4-naphthoquinone 300μM、myricetin 100μM、myricetin 300μM 127 Figure 4-39 酸性環境培養後樣品外觀:由左至右分別為control HγDC、chlorazol Black E 100μM、chlorazol Black E 300μM、5-hydroxy-1,4-naphthoquinone 100μM、5-hydroxy-1,4-naphthoquinone 300μM、myricetin 100μM、myricetin 300μM 128 Figure 4-40 酸性環境培養前後之ThT螢光檢測-小分子物質chlorazol Black E: (a)螢光全光譜 (b)485nm波長下強度 129 Figure 4-41 酸性環境培養前後之ThT螢光檢測-小分子物質myricetin: (a)螢光全光譜 (b)485nm波長下強度 131 Figure 4-42 酸性環境培養前後之ThT螢光檢測-小分子物質5-hydroxy-1,4-naphthoquinone: (a)螢光全光譜 (b)485nm波長下強度 132 Figure 4-43 酸性環境培養前後之tryptophan螢光光譜-小分子物質chlorazol Black E 134 Figure 4-44 酸性環境培養前後之tryptophan螢光光譜-小分子物質myricetin 135 Figure 4-45 酸性環境培養前後之tryptophan螢光光譜-小分子物質5-hydroxy-1,4-naphthoquinone 136 Figure 4-46 酸性環境培養前後之ANS螢光檢測-小分子物質chlorazol Black E: (a)螢光全光譜 (b)平均放射波長(A.E.W.) (c)平均放射波長下強度 139 Figure 4-47 酸性環境培養前後之ANS螢光檢測-小分子物質myricetin: (a)螢光全光譜 (b)平均放射波長(A.E.W.) (c)平均放射波長下強度 141 Figure 4-48 酸性環境培養前後之ANS螢光檢測-小分子物質5-hydroxy-1,4-naphthoquinone: (a)螢光全光譜 (b)平均放射波長(A.E.W.) (c)平均放射波長下強度 143 Figure 4-49 酸性培養前後之SDS-PAGE電泳(without β-Me) 144 Figure 4-50 酸性環境培養後之穿透式電子顯微鏡(TEM)圖: (a)control HGDC, 24hrs (b) chlorazol Black E 300μM, 24hrs (c) myricetin 300μM, 24hrs (d) 5-hydroxy-1,4-naphthoquinone 300μM, 24hrs 146 Figure 4-51 酸性培養前後之HγDC遠紫外光圓二色光譜圖 147 Figure 4-52(a)(b) 酸性培養前後之HγDC二級結構比例 149 Figure 4-53 HγDC與小分子物質於Binding site I的分子間作用力 (a)chlorazol Black E (b)myricetin (c)5-hydroxy-1,4-naphthoquinone 151 Figure 4-54 HγDC與小分子物質於Binding site II的分子間作用力 (a)chlorazol Black E (b)myricetin (c)5-hydroxy-1,4-naphthoquinone 152 Figure 4-55 HγDC與小分子物質於Binding site III的分子間作用力 (a)chlorazol Black E (b)myricetin (c)5-hydroxy-1,4-naphthoquinone 153 Figure 4-56 HγDC與小分子物質於Binding site IV的分子間作用力 (a)chlorazol Black E (b)myricetin (c)5-hydroxy-1,4-naphthoquinone 154 Figure 4-57 HγDC與小分子物質於Binding site V的分子間作用力 (a)chlorazol Black E (b)myricetin (c)5-hydroxy-1,4-naphthoquinone 155 Figure 5-1 小分子物質對於HγDC聚集之影響-紫外光部分結論圖 159 Figure 5-2 小分子物質對於HγDC聚集之影響-酸性部分結論圖 160 表目錄 Table 2-1 人類水晶體蛋白 6 Table 2-2 近年人類γD型水晶體蛋白的相關研究 20 Table 2-3 白內障之風險因素整理 31 Table 2-4 太陽輻射光譜之分類(ISO 21348) 33 Table 2-5 近年紫外光照射水晶體蛋白的相關研究 38 Table 2-6 近年酸性環境影響水晶體蛋白的相關研究 44 Table 2-7 分子抑制劑整理 48 Table 4-1 小分子物質之光散射下降百分比 86 Table 4-2 HγDC與小分子物質之對接能量(kJ/mol) 120 Table 4-3 HγDC與小分子物質之對接能量(J/g) 120 Table 4-4 HγDC(quadruple KN mutant)與小分子物質之分子間作用力整理 122 Table 4-5 小分子物質之ThT螢光下降百分比 133 Table 4-6 HγDC與小分子物質之對接能量(kJ/mol) 156 Table 4-7 HγDC與小分子物質之對接相互作用能量(kJ/mol) 156 | |
| dc.language.iso | zh-TW | |
| dc.title | 探討小分子物質對於人類γD型水晶體蛋白聚集之影響 | zh_TW |
| dc.title | Exploring the Effects of Small Molecules on the Aggregation of Human γD-Crystallin Protein | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 賴進此(Jinn-Tsyy Lai),侯劭毅(Shao-Yi Hou),林達顯(Ta-Hsien Lin),吳宛儒(Wan-Ru Wu) | |
| dc.subject.keyword | 白內障,人類γD型水晶體蛋白,小分子物質,蛋白質聚集,無定型體聚集體,類澱粉纖維, | zh_TW |
| dc.subject.keyword | cataract,human γD-crystallin,small molecule,protein aggregation,amorphous aggregate,amyloid fibril, | en |
| dc.relation.page | 186 | |
| dc.identifier.doi | 10.6342/NTU201901426 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2019-07-17 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-108-1.pdf 目前未授權公開取用 | 11.42 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。