G-Qudruplex Recognition and Stabilizing Agent: Synthesis of Fluorescent Carbazole Derivatives

• Main Authors: Shuo-Hung Hsu, 徐碩鴻
• Other Authors: Chao-Tsen Chen
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/14140057408118160365

碩士 === 國立臺灣大學 === 化學研究所 === 104 === G-qudruplex, a non-canonical four-stranded secondary structure which is composed of four-stranded guanine coplanar and stabilized by Hoogsteen hydrogen bondings and monovalent cations. In human genome, there are many DNA sequences are quinine-rich and have a tendency to form G-quadruplex. This special secondary structure can further regular the downstream bio-activities. In telomere, it hinders telomerase binding and prevent telomere from endless elongation; in oncogene promotor region, it impresses the transcription of oncogene. Base on these concepts, in this work we synthesized two BMVC derivatives: BMVC-2Cpy and dBMVC-3EG. UV and Fluorescence spectroscopy are used to discuss the photophysical properties of these ligands while interacting with various DNAs, the results show that both BMVC-2Cpy and dBMVC-3EG maintained their fluorescence turn-on function while binding with DNAs. The next step we use circular dichroism and fluorescence titration experiment to figure out whether BMVC-2Cpy and dBMVC-3EG can further stabilize sG-quadruplex, and it turns out that these ligands stabilized H26 and c-myc but the effect on H22 is unobvious. The sTRAP assay and laser confocal imaging were used to evaluate these ligand’s bio-application potential, and it seems that both two ligands can get into cancer cell’s nucleus and have an ability to suppress telomerase activity. In conclusion, we displayed that dBMVC-3EG has a entirely different fluorescence property while it interacts with double-strain DNA. Here we afford a new strategy to improve the ability of BMVC to be a G-quadruplex sensor.