Molecular Design and Evaluation of Artificial Gene Function-Regulating Agents in the Post-Genome Era

从化学和生物学的角度来看，光化学DNA切割剂的开发是非常有趣的，其通过在温和条件下用特定的光照射而选择性地切割DNA，并且没有任何添加剂，例如金属和还原剂，并且在医学上提供了相当大的潜力，特别是在后基因组时代。此外，使用光敏化药物的光动力疗法最近已经成为对抗癌症和相关疾病的有希望的方式。本课题设计并合成了蒽醌-碳水化合物、2-苯基喹啉-碳水化合物、喹啉-碳水化合物和β-咔啉-碳水化合物的人工杂化分子。此外，发现它们具有光诱导的DNA切割活性，具有DNA碱基或序列选择性。此外，喹喔啉-碳水化合物杂合体在UV照射后完全杀死HeLa S3细胞，而在没有光的情况下不发生作用。

The development of photochemical DNA cleaving agents, which selectively cleave DNA by irradiation with a specific light under mild conditions and without any additives such as metals and reducing agents, is very interesting from a chemical and biological standpoint and offers considerable potential in medicine especially in the post-genome era. Furthermore, photodynamic therapy using a photosensitizing drug has recently emerged as a promising modality against cancer and allied diseases. In this project, several artificial anthraquinone-carbohydrate, 2-phenylquinpline-carbohydrate, quinoxaline-carbohydrate, and β-carboline-carbohydrate hybrid molecules were designed and synthesized. Furthermore, it was found that they had light-induced DNA-cleaving activity with DNA base or sequence selectivity. In addition, the quinoxaline-carbohydrate hybrids completely kill HeLa S3 cells upon UV irradiation while no action occurs without light.