合成具噻吩環及吡啶環與netropsin衍生物偶合，來改變原本與DNA結合的位置，由A-T鹼基對轉換為G-C鹼基對；此外並改變所接的靜電基，利用其樹枝狀的架構，增加其立體效應，進而使凹槽結合試劑結合於大凹槽。

Synthetic netropsin analogs of the thiophene and pyridine, induce the netropsin analogs binding DNA from A-T base pair change to G-C base pair. Moreover, dendritic electrostatic groups have bulky conformation, which induce the netropsin analogs binding DNA to major groove.

第壹章 凹槽結合試劑與DNA凹槽結合模式

1-1前言 1
1-2抗癌藥物的分類 3
1-3凹槽結合試劑與DNA之結合模式 6
1-4聚醯胺官能基化合物對A-T鹼基對的排序選擇性 8
1-5 改變凹槽結合試劑的排序選擇性 12
1-5.1以咪唑環當氫鍵接受者 12
1-5.2以吡啶環當氫鍵接受者 14
1-5.3 以金屬離子當氫鍵接受者 15
1-6以連結試劑連接凹槽結合試劑 16
1-6.1 2：1結合模型 16
1-6.2側邊對側邊聚合 21
1-6.3頭對尾聚合 24
1-6.4頭對頭聚合 33
1-6.5尾對尾聚合 34
1-7 凹槽結合試劑的應用 35
1-7.1 凹槽結合試劑與金屬螯合試劑結合 35
1-7.2 凹槽結合試劑與細胞毒物結合 37
1-7.3 凹槽結合試劑與蛋白質結合 38
1-7.4 凹槽結合試劑與螢光發光體結合 40
1-8結論 41
1-9參考資料 43

第貳章 具芳香環之netropsin衍生物的合成探討

2-1合成動機 53
2-2合成具芳香環之netropsin衍生物 55
2-2.1 Netropsin前趨物的製備 55
2-2.2芳香環單酸的製備 61
2-2.3芳香環單酸與netropsin的前趨物聚合 68
2-3頭對頭聚合之netropsin衍生物 70
2-3.1芳香環雙酸的製備 70
2-3.2芳香環雙酸與netropsin的前趨物聚合 75
2-4生物活性比較 76
2-5 DNA熔點之測定 79
2-6結論 82
2-7實驗部份 84
2-8參考資料 139

第叁章 具多靜電基之netropsin衍生物的合成探討

3-1合成動機 143
3-2合成具含硫之多靜電基netropsin衍生物 144
3-2.1合成具含硫單靜電基netropsin衍生物 144
3-2.2合成具含硫雙靜電基netropsin衍生物 148
3-3合成具樹枝狀靜電基之netropsin衍生物 152
3-4合成具伸肼基之netropsin衍生物 160
3-5合成具2,2'-聯噻吩-嘧啶之netropsin衍生物 163
3-6結論 165
3-7實驗部份 167
3-8參考資料 195

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