Small-molecule discovery from DNA-encoded chemical libraries.
Small-molecule discovery from DNA-encoded chemical libraries.
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DOI：
10.1039/c1cs15076f
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发表时间：
2011-12
影响因子：
46.2
通讯作者：
Liu DR
中科院分区：
文献类型：
--
作者：
Kleiner RE;Dumelin CE;Liu DR
寻求提高生物活性小分子发现过程的效率和成本效益的研究人员最近接受了基于选择的方法，与传统的小分子筛选方法相比，该方法原则上提供更高的通量和更简单的基础设施要求。由于选择方法极大地受益于可以容易地扩增和解码的信息编码分子，一些学术和工业团体已经转向DNA作为文库编码的基础，并且在某些情况下，文库合成。所得到的DNA编码的合成小分子文库，与PCR的高灵敏度和超高通量DNA测序技术的最新发展相结合，可以非常快速地评估与目标靶的结合或键合形成，同时消耗最少量的材料，只需要适度的时间和设备投资。在这篇综述中，我们描述了两类方法的发展，用于编码的化学结构和与DNA的反应性：DNA记录的库合成，其中编码和库合成分别发生，和DNA指导的库合成，其中DNA编码和模板库合成。我们还描述了用于评估DNA编码库的体外选择方法，并总结了这些方法在发现生物活性小分子和新型化学反应性方面的成功应用。
Researchers seeking to improve the efficiency and cost effectiveness of the bioactive small-molecule discovery process have recently embraced selection-based approaches, which in principle offer much higher throughput and simpler infrastructure requirements compared with traditional small-molecule screening methods. Since selection methods benefit greatly from an information-encoding molecule that can be readily amplified and decoded, several academic and industrial groups have turned to DNA as the basis for library encoding and, in some cases, library synthesis. The resulting DNA-encoded synthetic small-molecule libraries, integrated with the high sensitivity of PCR and the recent development of ultra high-throughput DNA sequencing technology, can be evaluated very rapidly for binding or bond formation with a target of interest while consuming minimal quantities of material and requiring only modest investments of time and equipment. In this review we describe the development of two classes of approaches for encoding chemical structures and reactivity with DNA: DNA-recorded library synthesis, in which encoding and library synthesis take place separately, and DNA-directed library synthesis, in which DNA both encodes and templates library synthesis. We also describe in vitro selection methods used to evaluate DNA-encoded libraries and summarize successful applications of these approaches to the discovery of bioactive small molecules and novel chemical reactivity.
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