DNA编码化合物库技术用于药物筛选的策略进展

Strategy advance of DNA encoded compound library technology for drug screening

目的 综述DNA编码化合物库(DNA encoded compound library, DEL)技术用于药物筛选的策略进展。方法 检索国内外相关文献,根据筛选体系的不同对DEL筛选策略进行分类阐述。结果 DEL技术主要包括文库的构建、化合物的筛选和命中解码与重构化合物三个部分。其中,化合物的筛选技术作为DEL技术的中心环节已成为近年来的热门话题。为了扩增DEL技术应用的靶标范围,DEL筛选体系从最初的固相逐步发展成为液相,靶标体系从纯化蛋白逐步扩展到细胞裂解液和活细胞。近年来,DEL技术相继与多种现代技术联用,从基于亲和力的结合筛选转变到生化活性筛选,提高了筛选结果的准确性。结论 DEL筛选具有广阔的技术前景,研究者们正在为DEL筛选进行进一步的研究,预计未来能够继续取得更多实质性突破,用于更多药物的发现。

Objective To summarize the strategies of DNA-encoded compound library(DEL) technology for drug screening.Methods Relevant domestic and international literatures were searched, and DEL screening strategies were categorized and elaborated according to the different screening strategy.Results The DEL technology mainly included three parts: library construction, compound screening, and hit decoding and reconstitution.The technology of compounds had been a hot research topic in recent years.In order to expand the target scope of DEL screening strategies application, the initial solid-phase of the DEL screening system was developed to liquid-phase, and the target was gradually extended from purified proteins to cell lysates and even live cells.In recent years, various modern technologies were combined with DEL technology, and the affinity-based binding screening were converted to the biochemical activity screening.Conclusion DEL technology has a broad prospect, and many research groups and commercial companies are currently conducting further research for DEL screening.It is believed that more breakthroughs in DEL technology and more implementations in drug discovery will be achieved in the future.