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研究生:周峻名
研究生(外文):Jiyun-ming Jhou
論文名稱:雌二醇衍生物及其與雌激素受體鍵結分析
論文名稱(外文):Estradiol Derivatives and their Applications for Receptor Binding Assays
指導教授:陳淑慧陳淑慧引用關係
指導教授(外文):Shu-hui Chen
學位類別:碩士
校院名稱:國立成功大學
系所名稱:化學系碩博士班
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:2008
畢業學年度:96
語文別:中文
論文頁數:92
中文關鍵詞:雌激素雌激素受體雌二醇
外文關鍵詞:estrogenestrogen receptorestradiol
相關次數:
  • 被引用被引用:1
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雌激素影響著人體生長發展、體內平衡與細胞再生,許多雌激素引發的效應都是透過與雌激素受體鍵結而發生的。近幾年雌激素衍生化產物廣為應用在研究與雌激素受體鍵結。
本論文使用雌酮為起始物以合成17α取代的雌二醇衍生物,在雌酮的羰基行加成反應後生成支鏈,接著將支鏈末端活化轉換成疊氮基,再還原後可得帶有胺基支鏈的雌激素衍生物。透過此合成步驟可提升產率並減短反應步驟而有效率的合成雌激素衍生物。
在雌激素受體鍵結分析的應用,利用標定Cy3的衍生物可偵測固定在晶片上的ER,將雌激素衍生物修飾在PDMS基材以製成小分子晶片,初步結果顯示所合成的雌激素衍生物可與雌激素受體產生鍵結,證明所合成之衍生物具有與受體鍵結的活性。
Estrogens are known to influence the growth, development, homeostasis, and reproductive system of the human body. Many effects of estrogens are mediated through its binding to the estrogen receptor (ER). In recent years, estrogen derivatives were synthesized to develop bioassays for ER bindings.
In this research, we used estrone as the starting material to synthesize 17α substituted estradiol. After adding a side chain to the carbonyl group of estrone, the terminus of the added side chain was activated and then converted to azide group, and then converted to amino group via reduction reaction. The total reaction yield was increased and the reaction time was greatly reduced compared to the reported method. Thus, the synthesis method developed in this study is efficient.
The synthesized estrogen derivatives were applied for receptor binding assays. The derivatives were labeled with Cy3 fluorescence dye and then applied to bind with the immobilized ER on PDMS chips. Small molecule chip was fabricated by immobilizing the synthesized estrogen derivatives on PDMS substrates. Preliminary results indicated that the synthesized estradiol derivatives conserved the binding affinity with ER.
摘要 i
Abstract ii
謝誌 iii
目錄 iv
表目錄 vi
圖目錄 vii
英文縮寫對照表 viii
第一章:序論 1
第一節:雌激素與雌激素受體 1
第二節:微晶片與蛋白質晶片 13
第三節:研究動機 19
第二章:結果與討論 20
第一節:雌二醇的衍生化合成 20
第二節:衍生物與受體的鍵結分析 24
2-2-1:衍生物的鍵結測試 24
2-2-2:雌激素衍生物在蛋白質晶片的應用 30
2-2-3:雌激素衍生物在沈澱試驗的應用 34
第三節:結論 39
第三章:實驗部份與參考資料 41
第一節:一般實驗方法 41
第二節:化合物合成實驗方法及光譜資料 43
3-2-1:化合物5a之合成 43
3-2-2:化合物5b之合成 45
3-2-3:化合物6b之合成 47
3-2-4:化合物7b之合成 49
3-2-5:化合物8b之合成 51
3-2-6:化合物9b之合成 53
第三節:蛋白質晶片實驗方法 55
3-3-1:PDMS晶片製備及表面修飾 55
3-3-2:Cy3標定衍生物 57
3-3-3:蛋白質晶片測試衍生物的鍵結 58
3-3-4:蛋白質晶片偵測ERα實驗 59
第四節:沈澱試驗實驗方法 60
3-4-1:金奈米粒子製備及表面修飾 60
3-4-2:ERα的沈澱試驗實驗 61
參考文獻 62
附錄 67
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