DNA-encoded chemical libraries (DELs) have recently emerged and become an important technology platform in biomedical research and drug discovery. DELs containing large numbers of compounds can be prepared and selected against biological targets to discover novel ligands and inhibitors. In practice, DELs are usually selected against purified and immobilized proteins using the typical “bind–wash–elute” protocol; however, selection methods compatible with non-immobilized proteins would be able to greatly expand the target scope of DELs beyond purified proteins to more-complex and biologically relevant targets. Using a novel “ligate–cross-link–purify” strategy, we report here a method capable of selecting DELs against unmodified and non-immobilized protein targets. In addition, this method has shown excellent capability in identifying binders with moderate and weak affinities.

中文翻译：

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使用“连接-交联-纯化”策略选择针对非固定蛋白的DNA编码化学文库

DNA编码的化学文库（DEL）最近已经出现，并成为生物医学研究和药物发现中的重要技术平台。可以制备包含大量化合物的DEL，并针对生物学目标进行选择，以发现新的配体和抑制剂。在实践中，通常使用典型的“结合-洗涤-洗脱”方案针对纯化和固定化的蛋白选择DEL。但是，与非固定蛋白兼容的选择方法将能够将DEL的靶标范围从纯化蛋白扩展到更复杂且生物学相关的靶标。我们使用一种新颖的“连接-交联-纯化”策略，在此报告了一种能够针对未修饰的和未固定的蛋白质靶点选择DEL的方法。此外，