DNA-encoded chemical libraries (DELs) have emerged as a powerful technology in drug discovery. The wide adoption of DELs in the pharmaceutical industry and the rapid advancements of DEL-compatible chemistry have further fuelled its development and applications. In general, a DEL has been considered as a massive binding assay to identify physical binders for individual protein targets. However, recent innovations demonstrate the capability of DELs to operate in the complex milieu of biological systems. In this Perspective, we discuss the recent progress in using DNA-encoded chemical libraries to interrogate complex biological targets and their potential to identify structures that elicit function or possess other useful properties. Future breakthroughs in these aspects are expected to catapult DEL to become a momentous technology platform not only for drug discovery but also to explore fundamental biology.
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This work was supported by grants from the Research Grants Council of the Hong Kong Special Administrative Region, China (AoE/P-705/16, 17301118, 17111319, 17303220, 17300321 and C7005-20G), and from the National Natural Science Foundation of China (21572014, 21877093, 21907011 and 91953119), the Fundamental Research Funds for the Central Universities (project nos. 2020CQJQY-Z002 and 2021CDJYGRH-002) and Chongqing Research and Frontier Technology (cstc2020jcyj-jqX0009 and cstc2021jcyj-cxttX0002). We also acknowledge the funding support from the Laboratory for Synthetic Chemistry and Chemical Biology under the Health@InnoHK Program launched by the Innovation and Technology Commission, The Government of Hong Kong Special Administrative Region of the People’s Republic of China.
The authors declare no competing interests.
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Huang, Y., Li, Y. & Li, X. Strategies for developing DNA-encoded libraries beyond binding assays. Nat. Chem. 14, 129–140 (2022). https://doi.org/10.1038/s41557-021-00877-x
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