伪肽策略在DNA嵌插剂设计中的应用

Design of DNA intercalators:a strategy of pseudopeptides

DNA嵌插剂是临床上非常重要的一类抗肿瘤药物。在过去的几十年里,大量策略被用于DNA嵌插剂设计。其中伪肽策略由于高抗肿瘤疗效和低神经毒性而得到广泛关注。本文综述了伪肽策略的最新进展,包括结构多样性,三维定量构效关系,与DNA的分子对接,及一些评价抗肿瘤活性或嵌插分子机制的实用的物理化学方法,例如紫外光谱、荧光光谱、圆二色散光谱、DNA黏度和热变性温度实验研究方法。

In anti-tumor therapy DNA intercalators are of clinical importance.In the past few decades a number of strategies were used for intercalator design,of the reported strategies pseudo-peptides were specifically designed as a promising strategy,mainly due to their high anti-tumor efficacy and low neural toxicity.In this case,the present paper reviewed the recent progress of pseudo-peptides including their structural diversity,their 3D QSAR,and their docking towards DNA.To emphasize the utility some chemical physical methods either for evaluating the anti-tumor activity or for exploring the molecular mechanism,such as the UV,CD and fluorescence spectra,as well as the temperature melting and viscosity,which reflect the interaction of pseudo-peptide with DNA,were also mentioned.