Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3944
標題: Novel G-quadruplex DNA Recognizers: Asymmetric Organic Compounds
可辨識G-四股DNA結構的不對稱新分子
作者: 陳俊瑋
Chen, Jyun-Wei
關鍵字: 端粒
telomere
G-四股結構
共振衍生物
染色體
G-quadruplex
naphthalene-vinylpyridine conjugates
chromosome
出版社: 生醫工程研究所
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Blasco, Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nat. Genet. 2007, 39, 243-250. 15. Maizels Nancy, Dynamic roles for G4 DNA in the biology of eukaryotic cells, Nature structural & molecular biology, 2006, 13, 12, 1055-1059. 16. G. B. Morin, The human telomere terminal transferase is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell.1989, 59, 521-529. 17. H. Arthanari, S. Basu, T. L. Kawano and P. H. Bolton, Fluorescent dyes specific for quadruplex DNA. Nucleic Acids Res. 1998, 26, 3724-3728. 18. Cheng-Chung Chang, I.-Chun Kuo, I.-Fang Ling, Chin-Tin Chen, Huei-Chin Chen, Pei-Jen Lou, Jing-Jer Lin, and Ta-Chau Chang, Detection of Quadruplex DNA Structures in Human Telomeres by a Fluorescent Carbazole Derivative. Anal. Chem.. 2004, 76, 4490-4494. 19. G. N. Parkinson, M. P. H. Lee, S. Neidle, Crystal structure of parallel quadruplexes from human telomeric DNA. Nature. 2002, 417, 876-880. 20. Y. Wang, D. J. Patel, Solution structure of the human telomeric repeat d[AG3(T2AG3)3] G-tetraplex. Structure. 1993, 1, 262-283. 21. A. J. Zaug, E. R. Podell & T. R. Cech, Human POT1 disrupts telomeric G-quadruplexes allowing telomerase extension in vitro. Proc. Natl. Acad. Sci. 2005, 102, 10864-10869. 22. Y. Ishikawa, T. Yamashita, Y. Tomisugi, T. Uno, Interaction of porphyrins bearing peripheral cationic heterocycles with G-quadruplex DNA. Nucleic Acids Res Suppl. 2001, 1, 107-108. 23. D. Gomez, M. F. O''Donohue, T. Wenner, C. Douarre, J. Macadré, P. Koebel, M. J. Giraud-Panis, H. Kaplan, A. Kolkes, K. Shin-ya, J. F. Riou, The G-quadruplex ligand telomestatin inhibits POT1 binding to telomeric sequences In vitro and induces GFP-POT1 dissociation from telomeres in human cells. Cancer Research. 2006, 66, 6908. 24. Christopher M. Incles, Christoph M. Schultes, Helena Kempski, Heike Koehler, Lloyd R. Kelland and Stephen Neidle, A G-quadruplex telomere targeting agent produces p16-associated senescence and chromosomal fusions in human prostate cancer cells. Mol. Cancer Ther., 2004, 3, 1201-1206. 25. Cheng-Chung Chang, Jin-Yi Wu, Chih-Wei Chien, Wei-Sung Wu, Heng Liu, Chi-Chih Kang, Liang-Jye Yu, and Ta-Chau Chang, A Fluorescent Carbazole Derivative: High Sensitivity for Quadruplex DNA. Anal. Chem., 2003, 75, 6177-6183. 26. Cheng-Chung Chang, Jen-Fei Chu, Fu-Jen Kao, Yi-Chun Chiu, Pei-Jen Lou, Huei-Chin Chen, and Ta-Chau Chang, Verification of antiparallel G-quadruplex structure in human telomeres by using two-photon excitation fluorescence lifetime imaging microscopy of the 3,6-Bis(1-methyl-4-vinylpyridinium)carbazole diiodide molecule. Anal. Chem.. 2006, 78, 2810-2815. 27. Michael J Waring, Sequence-specific DNA Binding Agents, RSC Publishing, 2006. 28. Hao Wang, Charles A. 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摘要: 端粒的尾端單股序列DNA會形成一個四鹼基配對的平面結構,稱之為G-四股結構。在本研究中,我們合成出一系列以萘為主的共振衍生物,並將其用來辨識人類端粒序列d(T2AG3)4的四股結構。此類小分子會隨著與不同結構DNA作用後而有明顯的螢光變化,藉由此螢光表現可在光譜與電泳中區分出雙股結構DNA與四股結構DNA。綜合了光譜分析以及電泳實驗後,我們挑選出對於四股結構DNA有較佳選擇性以及鍵結能力的分子(IIb),進一步觀察細胞分裂中期染色體末端以及染色體其他區域受螢光分子染色後的螢光表現,我們發現在最接近端粒的區域有小分子-IIb的螢光顯現。綜合了這些結果,我們證實了人類端粒確實存在有四股結構的DNA,並利用螢光的特性使我們可清楚的看見端粒四股螺旋結構DNA的所在位置。
Single-stranded telomeric DNA tends to form a four-base-paired planar structure termed G-quadruplex. We have synthesized a series of naphthalene-vinylpyridine conjugates which can recognize specific quadruplex structure, essentially the quadruplex structure of human telomeric sequence d(T2AG3)4. The fluorescence intensity of these conjugates increases apparently upon interacting with various DNAs and this property can be used to discriminate between duplex and quadruplex DNAs. Together with analysis of spectrum and experiments about electrophoresis, we screen a compound - IIb, which present sensitivity and binding preference to quadruplex d(T2AG3)4 over duplex DNA. Furthermore, staining of compound IIb on the metaphase chromosomes bright fluorescence spots at telomere-proximal regions were revealed. Base on these results, we demonstrated that the presence of quadruplex structures in human telomeres with Flu. staining method.
URI: http://hdl.handle.net/11455/3944
其他識別: U0005-1608201100212600
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1608201100212600
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