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    Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/9211

    標題: 鳥糞嘌呤四合體之結合子並應用於鳥糞嘌呤四複合體的設計及合成
    Design and synthesis of G-quartet binders and applications toward G-quadruplex structures
    作者: 蕭泳助
    Yung-chu Hsiao
    貢獻者: 戴火木
    關鍵字: G四合體
    日期: 2007
    上傳時間: 2008-12-03 11:16:35 (UTC+8)
    摘要: 無止境的複製力及規避細胞衰亡的能力為惡性腫瘤細胞的顯著特性。而細胞的複製主要與端粒穩定有關,並且端粒的長短與細胞衰亡與否息息相關。在大多數的腫瘤細胞藉由端粒酶的活化來維持端粒的穩定性,在此的端粒酶為一種反轉錄酵素,主要用來催化端粒部份DNA的合成。而另一個使腫瘤細胞跳脫生命極限的機制則是藉由c-Myc致癌基因的異位表現,在此c-Myc的起始子部位有著一般的特徵為均含豐富鳥糞嘌呤(G)的DNA序列。因此能夠形成一種特別的二級結構稱G四複合體DNA結構(G-quadruplex)。在端粒部分DNA則與端粒及端粒酶弁酮袺騿A而在c-Myc的起始部位扮演調控轉錄的重要腳色。因此,G四合體有著雙重的機制來停控大部分腫瘤細胞的生長,更此,計畫利用結構相似性的機制來設計出新型的分子環四合胜肽引朵cyclo-tetra-[N-(1H-indol-5-carboxam-ide-3-yl)] (CTIn) 來針對G-quadruplexes部位來抑制癌細胞的生長。而最近有研究指出藉由一些有用的受質來穩定G-quadruplex 結構並用於治療及未來的研究具有相當的前景。
    The limitless replicative potential and their ability to escape senescence are prominent properties of malignant tumors. Cell replication is associated with the maintenance of telomeres and telomere shortening has been implicated in cellular senescence. Telomere maintenance that occurs in the majority of tumor cells is achieved through the reactivation of telomerase, a reverse transcriptase enzyme that catalyzes the synthesis of telomeric DNA. Another mechanism by which tumor cells achieve their immortality is via the ectopic expression of the c-Myc oncongene, a transcription factor that is intimately implicated in the control of cell proliferation and apoptosis. A common feature shared by the telomeric DNA and the promoter region in c-Myc is the presence of G-rich DNA sequences that are capable to adopt unusual secondary structures, called G-quadruplex DNA. The G-quadruplex structures in the telomeric DNA are thought to be involved in telomere and telomerase function, and the G-quadruplexes in the c-Myc promoter region play an important role in the control of the c-Myc transcription. Therefore, G-quadruplex structures represent a dual target to halt tumor growth across a broad spectrum of tumor types. Herein proposed is a structure-based approach to designing a novel molecule, cyclo-tetra-[N-(1H-indol-5-carboxam-ide-3-yl)] (CTIn), which may inhibit cancer growth by selectively interacting with G-quadruplexes. Recent advances in anticancer therapeutics through stabilization of the G-quadruplex structures by means of interacting ligands have shed light on our preliminary and future studies. Based on our existing knowledge on anticancer drug design, we will test the hypothesis that CTIn can exert pressure on cancer cell proliferation by targeting G-quadruplexes under three specific aims. Specific Aim design and synthesis of G-quartet binders.
    關聯: 校內校外均不公開
    Appears in Collections:[生物科技系(所)] 博碩士論文

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