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研究生:張栢綸
研究生(外文):Po-Lun Chang
論文名稱:氨基甲酸類抑制化合物對乙醯膽鹼酯酵素的三維定量結構活性關係研究
論文名稱(外文):3D quantitative structure-activity relationship studies of carbamates as inhibitors of acetylcholinesterase
指導教授:林家立林家立引用關係
指導教授(外文):Gia-Lih Lin
口試委員:謝定國錢偉鈞
口試日期:2015-01-08
學位類別:碩士
校院名稱:國立中興大學
系所名稱:化學系所
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:74
中文關鍵詞:乙醯膽鹼酯酵素氨基甲酸類抑制劑阿茲海默症
外文關鍵詞:acetylcholinesterase enzymecarbamate inhibitors
相關次數:
  • 被引用被引用:1
  • 點閱點閱:260
  • 評分評分:
  • 下載下載:19
  • 收藏至我的研究室書目清單書目收藏:0
乙醯膽鹼酯酵素(acetylcholinesterase enzyme)是治療阿茲海默症之主要標的物質,在本篇研究中,使用三維定量結構與活性關係(3D QSAR)計算,模擬50個氨基甲酸類抑制劑的抑制常數(KI)模型。其實驗結果呈現相當高度的相似度,且結果的R2值皆大於0.9,具統計學上之意義。透過對氨基甲酸類抑制劑模擬的分析結果,發現長鏈和苯的F2取代基對乙醯膽鹼酯酵素具有較佳的抑制效果。此研究結果可在未來設計氨基甲酸類抑制劑時,提供有效的資訊,以節省花費的時間與成本。
Acetylcholinesterase enzyme is the main topic of the treatment of Alzheimer's disease. In this study, I used a three-dimensional quantitative structure-activity relationship (3D QSAR) , to calculate the computer simulation models of 50 carbamate inhibitors inhibition constant (KI). The results presented a very high degree of similarity, and the R2 value results were all greater than 0.9, with statistical significance. Consequently, the results from the simulation of carbamate inhibitors presented that some long chains and phenyl F2 substituents got better inhibitory effect of the acetylcholinesterase enzyme. The results of this study provide a useful information in the future design of carbamate inhibitors, which could both save more time and reduce the costs it wasted.
摘要 I
Abstract II
謝誌 III
目錄 IV
圖目錄 VI
表目錄 VIII
第一章 緒論 1
1-1研究動機 1
1-2酵素(Enzyme) 2
1-2-1 活化位置(Active site) 3
1-2-2 鎖鑰模式(Lock-and-key model) 3
1-2-3 誘合模式(Induced-Fit model) 3
1-3酵素抑制劑 5
1-3-1 可逆抑制劑(Reversible inhibitor) 5
1-3-2 不可逆抑制劑(Irreversible inhibitor)[4-8] 16
1-4阿茲海默症(Alzheimer’s Disease) 18
1-5乙醯膽鹼與乙醯膽鹼酯酵素 19
1-5-1乙醯膽鹼酯酵素活性部位的結構與功能 20
1-5-2 乙醯膽鹼酯酵素的蛋白質結構與活性洞口 24
1-6乙醯膽鹼酯酵素抑制劑 25
1-7阿茲海默症(Alzheimer's Disease)的藥物治療 27
1-7-1 Tacrine (CognexR) 28
1-7-2 Donepezil (AriceptR) 29
1-7-3 Rivastigmine (Exelon R) 30
1-7-4 Galantamine (Razadyne R) 31
1-8抑制劑設計介紹 33
1-8-1 氨基甲酸 (Carbamate) 34
1-9電腦輔助藥物設計 36
1-9-1 3D QSAR 37
第二章 實驗材料及軟體操作 42
2-1本次研究使用的軟體 42
2-2 3D QSAR分析軟體 42
2-3 3D QSAR分析軟體操作 42
2-3-1 CoMFA & CoMISA[58] 42
2-3-2取代基基團虛擬篩選[58] 43
2-3-3分子對接 44
第三章 結果與討論 45
3-1比較分子場分析(CoMFA) 45
3-2比較分子相似性指數分析(CoMISA) 52
3-3易位體研究比較分子 場 分析(Topomer CoMFA) 62
第四章 結論 68
參考資料 69
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