具有 DNA 鍵結能力之天然物 Ditamycin 和 Netropsin 是做為設計 DNA 鍵結試劑之主要模板，幾個系列小分子化合物做為 DNA 鍵結試劑被成功合成後並完成了其生物物性測試。重氮聚醯胺雖表現較弱鍵結能力，但其具有光誘導切割DNA 以及識別鹼基對混合序列之能力。含醣類與重氮聚醯胺之化合物，亦呈現光誘導切割能力以及較佳之生物活性。喹啉化合物探討穩定四重鳥糞嘌呤因素，所得研究成果對穩定四重鳥糞嘌呤的鍵結試劑提供新策略。

Certain natural products, Ditamycin and Netropsin are considered as models of designing new DNA binding agents. A variety of DNA binding ligands were synthesized and accordingly characterized by different bioassays. In the series of azo-polyamide, it showed slight DNA binding affinity but has the properties of DNA photo-cleavage and recognition of mixed sequence. The carbohydrate-azo-polyamide series show the properties of DNA photo-cleavage and more effective in vitro experiment. In the quinoline series proves the attenuation effect for G-quadruplex stabilization which provides a novel strategy for development of G-quadruplex binding ligands.

第一章 序論
1-1 前言 1
1-2 雙股螺旋DNA 1
1-3 DNA小凹槽鍵結試劑
1-3-1 天然物 Netropsin 與 Distamycin 與 DNA小凹槽 3
1-3-2 吡咯環與咪唑環對 DNA 鹼基對之影響 4
1-4 醯胺鍵之異構化
1-4-1 新月構型之修飾 6
1-4-2 醯胺鍵之異構化 8
1-5 醣類對 DNA 之影響 9
1-6 四重鳥糞嘌呤 (G-quadruplex)
1-6-1 G-quadruplex 簡介 12
1-6-2 G-quadruplex 穩定試劑 13
1-7 結論 16
第二章 合成含重氮架橋之咪唑聚醯胺化合物與光解研究 2-1 研究動機與目的 17
2-2 合成研究與探討
2-2-1 Netropsin衍生物前驅物製備 19
2-2-2 具重氮官能基之 Netropsin衍生物製備 20
2-3 性質測試
2-3-1 DNA 熔點測定 22
2-3-2 一維 DNA 凝膠電泳 24
2-3-3 ESI 圖譜 27
2-3-4 Footprinting 實驗 28
2-4 結論 30
第三章
具重氮之DNA小凹槽試劑連接醣類官能基與光分解實驗
3-1 研究動機與目的 31
3-2 合成研究與探討
3-2-1 醣類化合物官能基修飾 32
3-2-2 Netropsin 衍生物前驅物製備 36
3-2-3 含醣類、重氮之 Netropsin 衍生物合成 37
3-3 性質測試
3-3-1 DNA 熔點測定 39
3-3-2 癌細胞實驗 42
3-4 結論 44
第四章
雙喹啉-咪唑小凹槽試劑與四重鳥糞嘌呤鍵結之控制因素
4-1 研究動機與目的 45
4-2 合成研究與探討
4-2-1 單喹啉主體與小凹槽試劑的合成討論 46
4-2-2 雙喹啉主體與小凹槽試劑的合成討論 50
4-3 性質測試
4-3-1 DNA 熔點測定 Calf-Thymus DNA (雙股螺旋) 52 4-3-2 DNA 熔點測定 G-quadruplex DNA 55
4-3-3 一維DNA 凝膠電泳. 59
4-4 結論 第五章 總結 60
第六章 實驗步驟 62
第七章 參考文獻 93

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