利用拉曼光譜研究富含鳥糞膘呤鹼基的端粒序列所形成的四股結構、雙股螺旋結構、以及血管增生調控序列所形成的四股結構在不同離子環境下,與3,6-bis (1-methyl-3- vinylpyrazinium) carbazole diiodide (BMVC-4)的作用模式差異

Investigation of binding differences of BMVC-4 with HT24、LD12、VEGF18 in different buffer condition by Raman spectroscopy

黃乙哲

指導教授 ： 張大釗

國立臺灣師範大學/理學院/化學系/碩士(2009年)

摘要

本實驗室所研發的3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC)是一個良好的四股結構穩定者,在細胞實驗下顯示其能有效抑制癌症細胞增生,而且與DNA作用後,其螢光性質會增強,所以亦可作為一個相當優良的螢光探針,為了研發更強而有利的四股結構穩定者,我們想要了解BMVC與DNA的作用模式為何?與不同結構的DNA的作用差異又是如何?所以我們利用拉曼光譜能以振動態角度去觀察兩物質作用機制的優勢,我們希望能由此得到更多有利的研發訊息,但由於螢光對於拉曼光譜而言是相當困擾的一件事,所以我們改採用結構類似但沒有螢光性質的3,6-bis(1-methyl -3- vinylpyrazinium) carbazole diiodide (BMVC-4),期望從分析其與DNA作用後的拉曼光譜差異,讓我們可以去模擬BMVC是如何與不同結構的DNA作用,並從中獲得有利訊息去研發更具潛力的新四股結構穩定者!

關鍵字

四股結構

並列摘要

Since last few decades, it is known that inhibition of telomerase ability is a key to suppress cancer cells proliferation. In the human telomeres, there is about 150-200bs single strand with (TTAGGG)n template repeats. Of particular interest is that the G-rich sequences can form G-quadruplex structures in the presence of monovalent cations such as Na+ and K+. Therefore, it is possible to stabilize the G-quadruplex for reducing the telomerase ability and then suppressing the cancer cells proliferation. Our laboratory have developed a novel G-quadruplex stabilizer, 3,6-bis(1-methyl-4-vinyl pyridinium) carbazole diiodide (BMVC), which can inhibit telomerase activity. In order to design a better G-quadruplex stabilizer, we intended to determine the binding mode of BMVC. Raman spectroscopy has the potential to investigate the detail binding mode at point of view from vibration motions. However the fluorescence of BMVC can be a serious problem upon interact with G-quadruplex. Here we choose 3,6-bis (1-methyl-3-vinyl pyrazinium) carbazole diiodide (BMVC-4)to do Raman experiment which is structural analogous to BMVC. BMVC-4 has negligible fluorescence interference even upon interact with DNA. Our experiment results allow us to investigage how BMVC-4 interacts with G-quadruplex, and of course, the binding mode. We believe that the realization of BMVC-4/G-quadruplex binding mode can provide important information for designing a better drug to suppress cancer cell proliferation.

並列關鍵字

G-quadruplex

參考文獻

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