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研究生:陳先文
研究生(外文):Shian-wen Chen
論文名稱:對DNA小凹槽鍵結的控制(一):咪唑的影響
論文名稱(外文):Controlling DNA Minor Groove Binding (I) : Influence of Imidazole
指導教授:王志偉王志偉引用關係
指導教授(外文):Chi-Wi Ong
學位類別:碩士
校院名稱:國立中山大學
系所名稱:化學系研究所
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:125
中文關鍵詞:小凹槽序列去氧核醣核酸鍵結聚醯胺
外文關鍵詞:sequenceminor grooveDNApolyamidebinding
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已知噻吩衍生物所具有細胞毒性,以及聚醯胺衍生物可以增加不同序列的辨識。因此,我們合成具有聯噻吩官能基與聚醯胺衍生物的化合物並測試其生物活性及鍵結的序列。
We synthesize polyamide compounds containing bithiophene functional group and lexitropsin analogs and study their biological activity.
第一章 具有生物活性的噻吩衍生物. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1

1-1 酵素CYP450活化噻吩的衍生物使其具有生物活性. . . . . . . . . . . . . . 1
1-2 藥物ticlopidine及clopidogrel對於心血管疾病的治療. . . . . . . . . . . . 3
1-3 抗腫瘤藥物-cyclopenta〔c〕thiphene. . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1-4 噻吩衍生物抑制微管蛋白(Tubulin)的聚合. . . . . . . . . . . . . . . . . . . . . 6
1-5 具有生物活性的天然物-5-(3-Buten-1-ynyl)-22''-bithienyl
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . .7
1-6 結論. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

第二章 近年來聚醯胺化合物之應用. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

2-1 結構的差異影響聚醯胺-螢光團(fluorophore)的複合物在細胞核
上的位置. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2-2 聚醯胺化合物在生物方面的應用. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16
2-2.1 聚醯胺與HIF(Hypoxia-inducible factor). . . . . . . . . . . . . . . . . . .16
2-2.2聚醯胺化合物與Human estrogen-related receptor 2(hERR2)
及Estrogen receptor α(hERα). . . . . . . . . . . . . . . . . . . . . . . . . . . . .22
2-2.3 Friedreich氏運動失調症與聚醯胺化合物. . . . . . . . . . . . . . . . . . .24
2.2.4聚醯胺化合物與human immunodeficiency virus type 1(HIV-1). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
2-3 人造的轉錄因子(synthetic transcription factor mimic)與
聚醯胺化合物. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2-4 增進聚醯胺對於DNA的鍵結強度及序列的選擇性. . . . . . . . . . . . . . .33
2-4.1 以稠環(fused ring)取代咪唑與吡咯. . . . . . . . . . . . . . . . . . . . . . .33
2-4.2 S型的聚醯胺化合物. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 34
2-4.3 合成新的聚醯胺化合物抑制NF-κB對DNA的鍵結. . . . . . . .35
2-5利用螢光放射光譜測定聚醯胺化合物的鍵結強度. . . . . . . . . . . . . . . . .37
2-6 結論. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .39

第參章 具芳香環之lexitropsin衍生物的合成探討. . . . . . . . . . . . . . . . 40

3-1 合成動機. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 40
3-2 合成具有聯噻吩環之lexitropsin衍生物. . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3-2.1 lexitropsin前驅物的製備. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3-2.2 聯噻吩環單酸的製備. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
3-2.3聯噻吩環單酸與lexitropsin的前驅物聚合. . . . . . . . . . . . . . . . . . .49
3-3 頭對頭聚合之lexitropsin衍生物. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
3-3.1聯噻吩環雙酸的製備. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .52
3-3.2芳香環雙酸與netropsin的前驅物聚合. . . . . . . . . . . . . . . . . . . . . . 53

第肆章 生物活性測試與DNA熔點測定. . . . . . . . . . . . . . . . . . . . . . . . . . . 55

4-1 DNA熔點的測定. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55
4-2細胞毒性測試. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

第伍章 結論. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

※附錄.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

一、儀器. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .73
二、溶劑. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .74
三、過程. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
四、實驗步驟. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
五、參考資料. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .102
1.Mosier, P. B.;Jurs, P. C., Chem. Res. Toxicol., 2003, 16, 721-732. (Predicting the Genotoxicity of Thiophene Derivatives from Molecular Stucture)
2.Richter, T.;Zanger, U. M., The Journal of Pharmacology and Experimental Therapeutics., 2003, 308, 189-197. (Potent Mechanism-Based Inhibition of Human CYP2B6 by Clopidogrel and Ticlopidine)
3.Dallemagne, P.;Khanh, L. P., Bioorganic&Medicinal Chemistry,. 2002, 10, 2185-2191. (Synthesis and Biological Evaluation of Cyclopenta[c]thiophene Related Compounds as New Antitumor Agents)
4.Romagnoi, R.;Baraldi, P. G., J. Med. Chem,. 2007, 50, 2273-2277. (Synthesis and Biological Evaluation of 2- and 3-Aminobenzo[b]thiophene Derivatives as Antimitotic Agents and inhibitors of Tubulin polymerization)
5.Hamel, E.;Lin C. M., Biochemistry, 1989, 28, 6984-6991. (Antimitotic Natural Products Combretastatin A-4 and Combretastatin A-2:Studies on the Mechanism of Their Inhibition of the Binding of Colchicine to Tubulin)
6.Rossi, R.;Carpita, A., Tetrahedron, 1984, 40, 2773-2779. (Palladium-Catalyzed Syntheses of Naturally-Occurring Acetylenic Thiophens and Related compound)
7.國立中山大學化學研究所碩士論文,馮誌遵,民國九十一年六月。 (雙噻吩衍生物的合成及生物活性研究)
8.Dervan, P. B.;Edelson, B. S., Nucleic Acids Research, 2004, 32, 2802-2818. (Influence of Structural Variation on Nuclear Localization of DNA-Binding Polyamide-Fluorophore Conjugates)
9.Dervan, P. B.;Olenyuk, B. Z., PNAS, 2004, 101, 16768-16773. (Inhibition of Vascular endothelial Growth Factor With a Sequence-Specific Hypoia Response Element Antagonist)
10.Dervan, P. B.;Viger, A., Bioorg. Med. Chem., 2006, 14, 8539-8549. (Exploring the Limits of Benzimidazole DNA-Binding Oligomers for the Hypoxia Inducible Factor(HIF)Site)
11.Dervan, P. B.;Nickols, D. G., Nucleic Acids Research, 2007, 35, 363-370. (Improved Nuclear Localization of DNA-Binding Polyamide)
12.Dervan, P. B.; Gearhart, M. D., Biochemistry, 2005, 44, 4196-4203.(Inhibition of DNA by Human Estrogen-Related Receptor 2 and Estrogen Receptor α with Minor Groove Binding Polyamide)
13.Dervan, P. B.; Burnett, R., PNAS, 2006, 103, 11497-11502. (DNA Sequence-Specific Polyamides Alleviate Transcription Inhibtion Associated with Long GAA.TTC Repeats in Friedreich’s Ataxia)
14.Ylisastigui, L.; Margolis, D. M., The Journal of Infectious Diseases, 2004, 190, 1429-1437. (Polyamides Reveal a Role for Repression in Latency within Resting T Cells of HIV-Infected Donors)
15.Dervan, P. B.; Uesugi, M., J.AM.CHEM.SOC., 2004, 126, 15940-15941.(Small Molecule Transcription Factor Mimic)
16.Kodadek, T.;Xiao, X., Journal of Combinatorial Chemistry, 2007 (Design and Synthesis of a Cell-Permeable Synthetic Transcription Factor Mimic)
17.Dervan, P. B.;Hauschild, K. E., PNAS, 2005, 102, 5008-5013.(Temperature-Sensitive Protein-DNA Dimerizers)
18.Spitzer, G. M.;Liedl, K. R., JACS, 2006. (DNA Minor Groove Pharmacophores Describing Sequence Specific Properties)
19.Heckel, A.;Famulok, M.;Brutschy, B., Angew. Chem. Int. Ed., 2007, 46, 4382-4384. (Polyamide Struts for DNA Architectures)

20.Dervan, P. B.;Wurtz, N. R., Biochemistry, 2002, 41, 7604-7609. (Inhibition of DNA Binding by NF-κB with Pyrrole-Imidazole Polyamides)
21.Dervan, P. B.;Chenoweth, D. M., bioorganic&Medicinal Chemistry, 2006, 15, 759-770. (Programmable Oligomer Targeting 5’-GGG-3’ in the minor groove of DNA and NF-κB Binding Inhibition)
22.Dervan, P. B.;Chenoweth, D. M., J. AM. CHEM. SOC., 2007, 129, 2216, 2217. (Fluorescent Sequence-Specific dsDNA Binding Oligomers)
23.Lown, J. W. Anti-Cancer Drug Des. 1988,3, 25.
24.Tor, Y.;Liu, Q., J. Org. Chem. 2004, 69, 8151-8153. (Synthesis of N-methylpyrrole and N-methylimidazole Amino Acids Suitable for Solid-Phase Synthesis)
25.Baird, E. E.; Dervan, Peter B. J. Am. Chem. Soc. 1996, 118, 6141. (Solid Phase Synthesis of Polyamides Containing Imidazole and Pyrrole Amino Acids
26.Xiao, J.; Yuan, G.; Huang, W.; Chan, A. S. C.; Lee, K. L. D. J. Org. Chem. 2000, 65, 5506. (A Convenient Method for the Synthesis of DNA-Recognizing Polyamides in Solution)

27.Nishiwaki, E.; Tanaka, S.; Lee, H.; Shibuya, M. Heterocycles 1988, 27, 1945. (Efficient Synthesis of Oligo-N-Methylpyrrolecarboxamides and Related Compounds)
28.Wynberg, H.; Bantjes, A. J. Org. Chem. 1959, 24, 1421. (Pyrolysis of Thiophene)
29.Kilbinger, A. F. M.; James Feast, W. J. Mater. Chem. 2000, 10, 1777. (Solution processable alternating oligothiophene-PEO-block-co- polymers: synthesis and evidence for solvent dependent aggregation)
30.Lown, J. W.; Krowicki, K.; Bhat, U. G.; Ward, B.; Dabrowiak, J. C. Biochemistry 1986, 25, 7408. (Molecular Recognition between Oligopeptides and Nucleic Acids : Novel Imidazole-Containing Oligopeptides Related to Netropsin That Exhibit Altered DNA Sequence Specificity)
31.Kissinger, K.; Krowicki, K.; Dabrowiak, J. C.; Lown, J. W. Biochemistry 1987, 26, 5590. (Molecular Recognition between Oligopeptides and Nucleic Acids. Monocationic Imidazole Lexitropsins That Display Enhanced GC Sequence Dependent DNA Binding)
32.Pelton, J. G.; Wemmer, D. E. Biochemistry 1988, 27, 8088. (Structural Modeling of the Distamycin A-d(CGCGAATTCGCG)2 Complex Using 2D NMR and Molecular Mechanics)
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