Design and synthesis of G-quartet binders and applications toward G-quadruplex structures

• Main Authors: Yung-chu Hsiao, 蕭泳助
• Other Authors: Huo-mu Tai
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/54006835476169427526

碩士 === 嘉南藥理科技大學 === 生物科技系暨研究所 === 95 === Abstract 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.