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裂解剂的发展是非常有趣的，它在医学上提供了相当大的潜力，特别是在后基因组时代。光化学DNA裂解剂在温和的条件下，通过特定的光照射选择性地裂解DNA，而不需要任何添加剂，如金属和还原剂。此外，使用光敏药物的光动力疗法最近已成为对抗癌症和相关疾病的一种有前途的方法。在本项目中，我们设计并合成了几种人工的蒽醌-碳水化合物、2-苯基喹啉-碳水化合物、喹恶啉-碳水化合物以及β-Caroline-碳水化合物杂化分子。此外，还发现它们具有光诱导的DNA裂解活性，具有DNA碱基或序列选择性。此外，喹恶啉-碳水化合物杂交物在紫外线照射下完全杀死HeLa S3细胞，而在没有光的情况下不发生任何作用。

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.