Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Waltham, Massachusetts 02451, USA.
Pharmaron, Inc., Boston, Massachusetts 02451, USA.
Nat Rev Drug Discov. 2017 Feb;16(2):131-147. doi: 10.1038/nrd.2016.213. Epub 2016 Dec 9.
DNA-encoded chemical library technologies are increasingly being adopted in drug discovery for hit and lead generation. DNA-encoded chemistry enables the exploration of chemical spaces four to five orders of magnitude more deeply than is achievable by traditional high-throughput screening methods. Operation of this technology requires developing a range of capabilities including aqueous synthetic chemistry, building block acquisition, oligonucleotide conjugation, large-scale molecular biological transformations, selection methodologies, PCR, sequencing, sequence data analysis and the analysis of large chemistry spaces. This Review provides an overview of the development and applications of DNA-encoded chemistry, highlighting the challenges and future directions for the use of this technology.
DNA 编码化合物库技术在药物发现中越来越多地被用于发现命中化合物和先导化合物。DNA 编码化学技术使人们能够探索比传统高通量筛选方法深四个数量级到五个数量级的化学空间。该技术的运作需要开发一系列能力，包括水性合成化学、砌块获取、寡核苷酸连接、大规模分子生物学转化、选择方法、PCR、测序、序列数据分析以及大型化学空间分析。本文综述了 DNA 编码化学技术的发展和应用，重点介绍了该技术应用面临的挑战和未来发展方向。
