20 years of DNA-encoded chemical libraries
20 years of DNA-encoded chemical libraries
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DOI：
10.1039/c1cc15634a
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发表时间：
2011-01-01
影响因子：
4.9
通讯作者：
Neri, Dario
中科院分区：
文献类型：
--
作者：
Mannocci, Luca;Leimbacher, Markus;Neri, Dario
识别特定的结合分子是化学、生物学和医学中的中心问题。因此，促进配基发现的技术可能大大有助于更好地了解生物过程和药物发现。DNA编码的化学文库代表了一种新的廉价的工具，可以快速有效地识别所选择的目标蛋白质的配体。这种文库由有机分子的集合组成，共价连接到一个独特的DNA标签上，作为一个可放大的识别条形码。DNA编码能够通过在几乎任何感兴趣的目标蛋白上以亚皮摩尔浓度的亲和力捕获来体外选择配体，类似于已建立的选择方法，如抗体噬菌体展示。几个学术和工业实验室已经研究了多种策略，以建立包含多达数百万DNA编码化合物的DNA编码化学图书馆。下一代高通量测序的实施使人们能够从前所未有的DNA编码文库中快速识别结合分子。本文回顾了DNA编码库技术的发展及其演变为一种新的药物发现工具，并对不同实验方法的挑战、前景和机遇进行了评论。
The identification of specific binding molecules is a central problem in chemistry, biology and medicine. Therefore, technologies, which facilitate ligand discovery, may substantially contribute to a better understanding of biological processes and to drug discovery. DNA-encoded chemical libraries represent a new inexpensive tool for the fast and efficient identification of ligands to target proteins of choice. Such libraries consist of collections of organic molecules, covalently linked to a unique DNA tag serving as an amplifiable identification bar code. DNA-encoding enables the in vitro selection of ligands by affinity capture at sub-picomolar concentrations on virtually any target protein of interest, in analogy to established selection methodologies like antibody phage display. Multiple strategies have been investigated by several academic and industrial laboratories for the construction of DNA-encoded chemical libraries comprising up to millions of DNA-encoded compounds. The implementation of next generation high-throughput sequencing enabled the rapid identification of binding molecules from DNA-encoded libraries of unprecedented size. This article reviews the development of DNA-encoded library technology and its evolution into a novel drug discovery tool, commenting on challenges, perspectives and opportunities for the different experimental approaches.