Taylor Cameron E, Roper Grace, Young Rhianna, Svensson Fredrik, Brunschweiger Andreas, Butterworth Sam, Leach Andrew G, Waring Michael J
Cancer Research Horizons Newcastle Drug Discovery Unit, Chemistry, School of Natural and Environmental Sciences, Newcastle University Bedson Building Newcastle upon Tyne NE1 7RU UK
Medical School, Newcastle University Framlington Place Newcastle upon Tyne NE2 4HH UK.
RSC Med Chem. 2025 Jul 29. doi: 10.1039/d5md00350d.
DNA-encoded libraries (DELs) are established as an effective screening strategy to identify protein ligands and offer a cost-effective means of screening large numbers of compounds. However, the synthesis and utilisation of DELs is implemented by relatively few laboratories. Here, we describe the design and synthesis of a medium-sized DEL through simple amide coupling procedures. We provide details of chemistry and enzymatic steps and demonstrate their effectiveness by synthesising 300 thousand and 3 million-member DELs. We demonstrate their integrity through screening against carbonic anhydrase IX and show their chemical diversity through comparison with an established high-throughput screening library. The DELs described can be used as a resource to accelerate hit identification for early-phase drug discovery and are available to the academic community for screening.
DNA编码文库（DELs）已成为一种有效的筛选策略，用于鉴定蛋白质配体，并提供一种经济高效的方法来筛选大量化合物。然而，DELs的合成和应用仅由相对较少的实验室实施。在此，我们描述了通过简单的酰胺偶联程序设计和合成一个中等规模的DEL。我们提供了化学和酶促步骤的详细信息，并通过合成30万和300万成员的DELs证明了它们的有效性。我们通过针对碳酸酐酶IX进行筛选来证明它们的完整性，并通过与已建立的高通量筛选文库进行比较来展示它们的化学多样性。所描述的DELs可作为一种资源，用于加速早期药物发现中的活性化合物鉴定，并可供学术界用于筛选。
