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論文名稱 Title |
對DNA小凹槽鍵結的控制(一):咪唑的影響 Controlling DNA Minor Groove Binding (I) : Influence of Imidazole |
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系所名稱 Department |
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畢業學年期 Year, semester |
語文別 Language |
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學位類別 Degree |
頁數 Number of pages |
125 |
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研究生 Author |
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指導教授 Advisor |
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召集委員 Convenor |
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口試委員 Advisory Committee |
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口試日期 Date of Exam |
2007-06-21 |
繳交日期 Date of Submission |
2007-07-17 |
關鍵字 Keywords |
小凹槽、序列、去氧核醣核酸、鍵結、聚醯胺 sequence, minor groove, DNA, polyamide, binding |
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統計 Statistics |
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中文摘要 |
已知噻吩衍生物所具有細胞毒性,以及聚醯胺衍生物可以增加不同序列的辨識。因此,我們合成具有聯噻吩官能基與聚醯胺衍生物的化合物並測試其生物活性及鍵結的序列。 |
Abstract |
We synthesize polyamide compounds containing bithiophene functional group and lexitropsin analogs and study their biological activity. |
目次 Table of Contents |
第一章 具有生物活性的噻吩衍生物. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1 1-1 酵素CYP450活化噻吩的衍生物使其具有生物活性. . . . . . . . . . . . . . 1 1-2 藥物ticlopidine及clopidogrel對於心血管疾病的治療. . . . . . . . . . . . 3 1-3 抗腫瘤藥物-cyclopenta〔c〕thiphene. . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1-4 噻吩衍生物抑制微管蛋白(Tubulin)的聚合. . . . . . . . . . . . . . . . . . . . . 6 1-5 具有生物活性的天然物-5-(3-Buten-1-ynyl)-22'-bithienyl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . .7 1-6 結論. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 第二章 近年來聚醯胺化合物之應用. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9 2-1 結構的差異影響聚醯胺-螢光團(fluorophore)的複合物在細胞核 上的位置. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2-2 聚醯胺化合物在生物方面的應用. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16 2-2.1 聚醯胺與HIF(Hypoxia-inducible factor). . . . . . . . . . . . . . . . . . .16 2-2.2聚醯胺化合物與Human estrogen-related receptor 2(hERR2) 及Estrogen receptor α(hERα). . . . . . . . . . . . . . . . . . . . . . . . . . . . .22 2-2.3 Friedreich氏運動失調症與聚醯胺化合物. . . . . . . . . . . . . . . . . . .24 2.2.4聚醯胺化合物與human immunodeficiency virus type 1(HIV-1). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2-3 人造的轉錄因子(synthetic transcription factor mimic)與 聚醯胺化合物. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 2-4 增進聚醯胺對於DNA的鍵結強度及序列的選擇性. . . . . . . . . . . . . . .33 2-4.1 以稠環(fused ring)取代咪唑與吡咯. . . . . . . . . . . . . . . . . . . . . . .33 2-4.2 S型的聚醯胺化合物. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 34 2-4.3 合成新的聚醯胺化合物抑制NF-κB對DNA的鍵結. . . . . . . .35 2-5利用螢光放射光譜測定聚醯胺化合物的鍵結強度. . . . . . . . . . . . . . . . .37 2-6 結論. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .39 第參章 具芳香環之lexitropsin衍生物的合成探討. . . . . . . . . . . . . . . . 40 3-1 合成動機. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 40 3-2 合成具有聯噻吩環之lexitropsin衍生物. . . . . . . . . . . . . . . . . . . . . . . . . . . 41 3-2.1 lexitropsin前驅物的製備. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 3-2.2 聯噻吩環單酸的製備. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 3-2.3聯噻吩環單酸與lexitropsin的前驅物聚合. . . . . . . . . . . . . . . . . . .49 3-3 頭對頭聚合之lexitropsin衍生物. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 3-3.1聯噻吩環雙酸的製備. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .52 3-3.2芳香環雙酸與netropsin的前驅物聚合. . . . . . . . . . . . . . . . . . . . . . 53 第肆章 生物活性測試與DNA熔點測定. . . . . . . . . . . . . . . . . . . . . . . . . . . 55 4-1 DNA熔點的測定. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55 4-2細胞毒性測試. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 第伍章 結論. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 ※附錄.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 一、儀器. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .73 二、溶劑. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .74 三、過程. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 四、實驗步驟. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 五、參考資料. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .102 |
參考文獻 References |
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