Design and Synthesis of New Diazene-Isosteric DNA Minor Groove Binding Agent

• Main Authors: Yen-ming Chou, 周彥鳴
• Other Authors: Chi-Wi Ong
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/24575127738228073145

碩士 === 國立中山大學 === 化學系研究所 === 104 === Natural products Distamycin and Netropsin, an oligopyrrole-amide have been reported to bind strongly with the A-T base pairs on the DNA minor groove. In order to allow specific base pair recognition for more diverse duplex DNA sequences, whereby promoting their potential applications as genomic drugs in the pharmaceutical chemistry, much research has centered on the modification of the pyrrole ring to make them G-C selective and improve binding affinity. 　　Less work have focused on changing the bridging amide functional group to achieve DNA sequence specificity and binding affinity. The first bridging azo functional group has been introduced to interconnect the pyrrole rings as model compound of Distamycin has been reported by our lab, and was found to successfully increase the recognition ability for G-C base pairs. In this thesis, we dedicate our effort to overcome the difficulties encounter during the previous synthesis of, and try to synthesize multiple azo- linkage between the pyrrole rings. 　　Finally, although the attempt failed, we have incorporated the amide-pyrrole with the azo group, but having a configuration somewhat inconsistent with the traditional crescent-shaped minor groove DNA binding agents. Preliminary DNA melting temperature assay studies with calf thymus DNA found that this kind of compounds have a better ability to stabilize the duplex DNA.