毛细管电泳药物筛选方法与技术

毛细管电泳（CE）在新药研发领域显示着重要的应用前景。CE使用水溶液介质作为实验体系，保证了药物筛选在类似于生命介质的环境中进行，优于其他传统体外仪器筛选方法。除了维持被筛选分子和作用对象的生物活性外，CE筛选过程着重突出配体与受体之间的相互作用。毛细管电泳药物筛选瞄准与药理学理论相关的重要参数，如结合常数K_b 、结合速率常数K_on 和解离速率常数K_off ，有利于模拟并预测机体内靶标与药物之间的相互作用过程。该文回顾了毛细管电泳进行药物筛选的历史，评述了毛细管电泳药物筛选方法所依据的理论和相对成熟的各种常用方法，并抽取了部分典型实例以及相关技术进行说明，对以亲和毛细管电泳、动力学毛细管电泳为手段的药物筛选方法进行了介绍，包括分子和细胞层次的药物筛选，以及针对不同类型的候选药物的研究工作都有提及。毛细管电泳与多种技术的联用，包括与质谱以及化学发光等联用发挥了更大的效能。联用方法还应用于中药有效成分的筛选。毛细管电泳在DNA编码化合物库筛选中将有良好应用前景。馏分收集的发展为筛选药物提供了广阔前景，它配合指数富集配体系统进化技术为毛细管电泳药物筛选提供了更多可能。总之，毛细管电泳多样可选的药物筛选方法和技术将为新概念的药物筛选与药物评价提供有力支撑。

Methods and techniques of capillary electrophoresis for drug screening

Capillary electrophoresis (CE) shows enormous potential for application in new drug research and development. Because of the aqueous medium employed as the running buffer in CE, drug screening can be carried out in an environment similar to that in physiological testing media. Drug screening methods based on CE are different from other instrumental measurements in vitro. CE can not only sustain the biological activity of the screened molecules and ligands, but also help evaluate the interactions between the receptors and the ligands. Based on these interactions, some important pharmacological parameters related to drug screening, such as the association constant K_b , bonding rate constant K_on , and dissociation rate constant K_off , can be determined by CE. Thus, CE is an effective tool for simulating and predicting the entire interaction process between receptors and drugs in vivo. In this review, the history of CE for drug screening is revisited. The theories, common methods for drug screening by CE, and some application examples and related technologies are reviewed. The methods of drug screening by means of affinity CE and kinetic CE are introduced. Some selected studies on different ligands at the molecular and cellular level are reported, along with examples several types of drugs. Techniques based on a combination of CE with mass spectrometry and chemiluminescence are reviewed, with focus on the screening of candidate drugs and active compounds from traditional Chinese medicine. The application prospect of drug screening by CE combined with a DNA-encoded compound library is introduced. This paper discusses the core of the fraction collection step in CE and emphasizes the significance of combining CE with systematic evolution of ligands by exponential enrichment. In conclusion, various optional methods for CE drug screening would pave the way for new concepts related to drug screening and evaluation in the future.