【作者】 周秋菊； 李林； 向俊锋； 唐亚林；

【Author】 Qiuju Zhou Lin Li Junfeng Xiang Yalin Tang Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China

【机构】 中国科学院化学研究所；

【摘要】 开发一种简单的、高效的从天然植物提取物中快速筛选出高生理活性化合物的方法是目前全球药物研发的热点问题。本课题组提出了一种全新的基于DNA靶分子特异性识别和核磁共振技术对天然植物中抗肿瘤活性成分进行快速筛选和结构鉴定的一体化方法:即在植物提取物体系中引入DNA靶分子,利用生物靶分子对其配体的特异性识别作用获取配体核磁共振谱学信息,从而获得被DNA靶分子识别化合物结构。这一方法的具体过程是:利于DNA靶分子G-四链体亚胺基质子化学位移变化作为判断植物提取物中是否含有活性成分的标识,然后利用扩散序谱对结合到靶分子上的配体分子虚拟分离,得到其特征谱峰,再进一步利用氢氢相关以及氢碳相关来确认配体分子骨架的信号,从而推测出配体分子结构。应用这种策略可以实现从复杂的天然抗肿瘤植物或者药方提取物中快速筛选出活性成分并完成结构鉴定。更多还原

【Abstract】 The development of a simple and efficient method,which allows to fast screen compounds with high biological activity from natural plant extracts,is an attractive field in drug discovery. Our group propounded a novel strategy for fast screening and structural identification of antitumor agents from natural plant extracts by coupling the DNA target molecule’s recognition with NMR techniques.That is to say,by introduction of DNA target molecule into natural plant extracts,the ligand(s)in the extracts will be recognized by target molecule and therefore can be monitored by NMR techniques.Our tactics includes the following three steps:judging the existence of G-quadruplex ligand(s)in the test extracts by ~1H NMR spectra;detecting the characteristic peak(s) of G-quadruplex ligand(s)using DOSY NMR methods;and subsequently identifying the structure of G-quadruplex ligand(s)by 2D NMR experiments such as HSQC and HMBC.Our work provides a very promising strategy to fast screen lead components or antitumor agents from natural plant extracts.更多还原