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研究生:黃雯英
論文名稱:三環衍生物抑制劑的計算與構形分析
論文名稱(外文):Calculations and Conformations of Cyclopropane-Derived Inhibitors
指導教授:蘇世剛
指導教授(外文):Shyn-Gang Su
學位類別:碩士
校院名稱:國立成功大學
系所名稱:化學系
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:2001
畢業學年度:90
語文別:中文
論文頁數:107
中文關鍵詞:抑制劑三環酵素構形
外文關鍵詞:inhibitorcyclopropaneenzymeconformation
相關次數:
  • 被引用被引用:0
  • 點閱點閱:237
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  • 下載下載:23
  • 收藏至我的研究室書目清單書目收藏:0
我們以AM1(Austin Model)量子計算方法,探討三環化合物inhibitor pepdiomimetics的生化活性,特別是比較 以三環與非 三環 組成骨幹主鍊的抑制劑間生化活性的差異。由計算結果顯示,cyclopropane 衍生物具有比雙鍵分子更大的torsional energy,而如此高的torsional energy 也是造成cyclopropanes 衍生而成的 peptides mimics 形成固定構形的主要因素。
根據對不同抑制劑構形分析發現,支鏈不同的取代基容易影響非三環抑制劑肽鏈主鏈的構形,而且主鏈末端取代基的種類,會對主鏈的構形造成影響,但peptidomimetics因有三環固定構形,主鏈受到末端取代基的變化遠小於peptide。整個非三環化合物分子構形容易捲曲以利分子內氫鍵的形成,當此分子沒有機會形成分子內氫鍵時,整個構形亦可能以展開的形式存在。
對分子構形與生化活性的分析結果發現,由於三環造成分子主鏈骨幹形成類似 C 形結構,固定主鏈構形,使其不易隨著支鏈單鍵易旋轉的特性改變主鏈構形,僅末端單鍵鍵結的位置易自由扭動。以三環組成骨幹主鏈的抑制劑,因為不容易扭動,因此生成容易與enzyme active site結合的特殊結構,成為高活性的抑制劑,然而三環抑制劑卻也可能因它的構形與enzyme active site 的契合度不好,降低它與酵素結合的機會。

We use AM1(Austin Model)quantum mechanical calculation methods to discusss the biochemistry activity of cyclopropane-derived inhibitor peptidomimetics , especially to compare the differences of biochemistry activity between inhibitors which are composed of cyclopropane and of uncyclopropane in the main chain 。
In the results of calculations,cyclopropane-derived inhibitors have higher torsional energy than moleculars with double bonds, and such a high torsional energy is the main reason which makes cyclopropane-derived peptidomimetics conformations rigid。
According to the analysis of different kinds of conformations in inhibitors , we discover that the kinds of end subsitutents in the main chain will affect the conformation of main chains,too。
Because peptidomimetics have rigid conformation with cyclopropane , the end-substitutes affect main chain much less than Peptides。The whole conformation of peptides curves easily , and this helps to form intramolecular hydrogen bonds ,when those compounds cannot form intramoleclar hydrogen bonds, the whole conformation may also probably exist in a stretching form。
From the results of analysis of molecular conformations and biochemctistry activity,we discover that of cyclopropane molecular main chains form “C”structures to make main chains have a rigid conformation, only the final place in the main chain rotates with single bonds easily。
It is hard to rotate the main chains of cyclopropane-derived inhibitors, so it brings that a special conformations which binds with enzyme active site easily, becomes highly active inhibitors。But when the conformation of cyclopropane-derived inhibitors are not compatible with enzyme active site, this reduces its activity to bind with enzyme active sites。

目錄
第一章簡介
1-1cyclopropane的性質…………………...2
1-2cyclopropane衍生物在各方面的應用…………...5
1-3 研究目標與方向………………………………………11
第二章三環化合物與非三環化合物的結構分析
2-1 簡介……………………………………………….14
2-2 分析原理…………………………………………21
2-3 分析方法…………………………………………22
2-4 分析結果……………………………………………....25
2-5結論………………………………………..36
第三章單三環化合物與非三環化合物的構形分析
3-1前言……………………………………………38
3-2分析原理與方法…………………………………39
3-3 a1、a2系列peptidomimetics與 dipeptide的構形分析……..40
3-4 a5系列collagnase inhibitor 的構形分析………………. 45
3-5 a6系列rein inhibitor 的構形分析……………………….50
3-6 Purine nucleoside phosphorylase inhibitor活性分析…..54
3-7 結論………………………………………………………………55
第四章雙三環化合物與非三環化合物的構形分析
4-1 a7系列雙三環化合物與非三環化合物的構形分析…………58
4-2a8系列雙三環化合物與非三環化合物的構形分析…...70
4-3結論……………………………………………………80
第五章支鏈對三環化合物與非三環化合物的構形影響分析
5-1 支鏈對a6系列三環化合物與非三環化合物的構形影響分析...83
5-2支鏈對a7-5雙三環化合物與a7-7非三環化合物的構形分析..92
5-3結論………………………………………………………..100
結論………………………………………………………………………103
參考文獻………………………………………………………………...106

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