Department of Chemistry and State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
Department of Chemistry and State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China; Department of Chemistry, Southern University of Science and Technology, 1088 Xueyuan Road, Shenzhen, 518055, China.
Biochem Biophys Res Commun. 2020 Dec 3;533(2):215-222. doi: 10.1016/j.bbrc.2020.04.033. Epub 2020 Apr 29.
DNA-encoded chemical library (DEL) has emerged as a powerful technology for ligand discovery in biomedical research. Recently, we have developed a DNA-encoded dynamic library (DEDL) approach by incorporating the concept of dynamic combinatorial library (DCL) with DELs. DEDL has shown excellent potential in ligand discovery towards a variety of protein targets. However, the requirement of having a pair of unnatural p-stilbazoles as the interstrand DNA crosslinker has limited the chemical diversity of DEDLs. Here, we replaced p-stilbazole with psoralen (PS) and tested the feasibility of psoralen as the crosslinker in DEDL selection. Since psoralen is commercially available and does not require any special crosslinking partner, existing DELs may be directly used to create high-diversity DEDLs. This study is expected to greatly facilitate the development of DEDLs as a versatile tool in drug discovery.
DNA 编码化合物库 (DEL) 已成为生物医学研究中配体发现的强大技术。最近，我们通过将动态组合化学库 (DCL) 的概念与 DEL 相结合，开发了 DNA 编码动态库 (DEDL) 方法。DEDL 在针对各种蛋白质靶标的配体发现方面显示出了优异的潜力。然而，需要一对非天然的 p-联苯唑作为链间 DNA 交联剂，限制了 DEDL 的化学多样性。在这里，我们用补骨脂素 (PS) 取代了 p-联苯唑，并测试了 PS 作为交联剂在 DEDL 选择中的可行性。由于补骨脂素是商业上可获得的，并且不需要任何特殊的交联伙伴，现有的 DEL 可以直接用于创建高多样性的 DEDL。这项研究有望极大地促进 DEDL 作为药物发现的多功能工具的发展。
