研究生: |
曹雅萍 |
---|---|
論文名稱: |
棘黴素與核三結合機轉之探討 |
指導教授: | 黃文彰 |
學位類別: |
碩士 Master |
系所名稱: |
化學系 Department of Chemistry |
畢業學年度: | 85 |
語文別: | 中文 |
論文頁數: | 132 |
中文關鍵詞: | 棘黴素 |
英文關鍵詞: | Echinomnycin |
論文種類: | 學術論文 |
相關次數: | 點閱:227 下載:0 |
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棘黴素(Echinomnycin)為quinoxaline族中具有抗腫瘤功效之藥物。由Dervan等人利用化學足跡法發現,echinomycin對於以d(CG)為中心之四個鹼基對大小之序列其有最強的結合能力。至目前為止,大部分對此複合物的結構生物學研究,多僅針對具有迴文對稱性序列的DNA來做探討,以舒緩其複雜性。但由於棘黴素(echinomycin)本身並非一個完全對稱的結構,為了瞭解非迴文對稱性序列DNA與echinomycin結合成複合物後,是否會有不同結構的複合物產生,因而採用序列為[d(CCGC).d(GCGG)]的不對稱寡核苦酸作進一步的採討。實驗結果發現,Quinoxaline ring插入DNA後,形成兩組比例相當的複合物,這兩組化合物中,有關DNA的部份差異並不大,至於棘黴素(echinomnycin)的方位則相差比180°。兩者穩定性相當,皆以氫鍵、凡得瓦力、及鹼基間堆疊的作用力來穩定結構。而結構部份,則發現DNA為B-form like的形式,且所有的鹼基均以反式構形存在。棘黴素(echinomycin)結合前後結構變異不大,與游離狀態下類似。
Echinomycin, including its analogs such as triostin A, luzopeptin... etc., is probably the most well defined model system in terms of the binding sites specificity. It is worthy to note that all previous works, describing conformational features of echinomycin binding complex in atomic resolution, were utilized the same two palindromic binding sites namely [d(ACGT)]2 and [d(TCGA)]2. Nonetheless, the only model system capable to reveal the nature of binding specificity is to use a non-palindromic binding sites by realizing the lacking of an exact two-fold symmetry of echinomycin molecule itself. Here, we propose to study another non-palindromic sequence, namely [d(CCGC).d(GCGG)], the only strong echinomycin binding site with G/C instead of A/T proceeding and after the intercalating d(CG) step.