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药物靶点的鉴定和相关研究在药学研究领域具有重要的理论指导意义和实用价值。利用亲和探针偶联靶分子的方法是目前发现药物靶点的主要手段之一。该方法可从分子水平发现药物的作用靶点,从而对药物的分子作用机制提供细胞水平的直接证据。从DNA和小分子药物探针的构筑和应用入手,对近些年鉴定DNA损伤识别蛋白的研究进展进行了较为详尽的讨论,并简要介绍目前探索小分子药物作用靶点的主流技术。作为亲和偶联鉴定药物作用靶点方法的重要组成部分,亲和探针设计的合理性关系到方法本身的可操作性以及鉴定结果的可靠性。从多个角度对DNA探针和小分子药物探针的设计经验进行了较为系统的总结,例如经典的亲和纯化分离方法,以及更为高效的光激发共价偶联技术等。这些方法和思路为探索DNA损伤相关蛋白质的功能以及小分子药物的细胞作用机制提供了丰富的研究工具,有助于从分子水平理解药物的作用机制。
Identification of drug targets and related research in the field of pharmacy has important theoretical significance and practical value. The method of coupling the target molecule with the affinity probe is one of the main methods for finding the drug target. This method can be used to find the target of drug action at the molecular level and provide direct evidence of the cellular level of the molecular mechanism of action of the drug. Starting with the construction and application of DNA and small molecule drug probes, the progress in the identification of DNA damage recognition proteins in recent years is discussed in detail. The current mainstream technologies for exploring the target of small molecule drugs are briefly introduced. As an important part of the method of affinity coupling to identify drug targets, the rationality of affinity probe design is related to the operability of the method itself and the reliability of the identification results. The design experience of DNA probes and small molecule drug probes has been systematically summarized from many aspects, such as classical affinity purification separation method and more efficient light-induced covalent coupling technology. These methods and ideas provide a rich research tool for exploring the function of DNA damage-related proteins and the cellular mechanism of small molecule drugs, and help to understand the mechanism of action of drugs at the molecular level.