期刊
CHEMBIOCHEM
卷 22, 期 14, 页码 2384-2397出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202100144
关键词
DNA-encoded library; High throughput screening; Drug discovery; Ligand discovery; Combinatorial library
资金
- Research Grants Council [AoE/P-705/16, 17321916, 17302817, 17301118, 17111319, 17303220]
- National Natural Science Foundation of China [21572014, 21877093, 91953119]
- Laboratory for Synthetic Chemistry and Chemical Biology under the Health@InnoHK Program
- Government of Hong Kong Special Administrative Region of the People's Republic of China
DNA-encoded libraries (DEL) have become a major technology platform for ligand discovery in academia and the pharmaceutical industry, with advancements in technology and chemistries leading to improved chemical diversity and expanded target scope. Innovations in DEL selection methods have not only broadened the applications of DELs, but also demonstrated their potential as a powerful tool in exploring fundamental biology.
DNA-encoded libraries (DEL) have come of age and become a major technology platform for ligand discovery in both academia and the pharmaceutical industry. Technological maturation in the past two decades and the recent explosive developments of DEL-compatible chemistries have greatly improved the chemical diversity of DELs and fueled its applications in drug discovery. A relatively less-covered aspect of DELs is the selection method. Typically, DEL selection is considered as a binding assay and the selection is conducted with purified protein targets immobilized on a matrix, and the binders are separated from the non-binding background via physical washes. However, the recent innovations in DEL selection methods have not only expanded the target scope of DELs, but also revealed the potential of the DEL technology as a powerful tool in exploring fundamental biology. In this Review, we first cover the classic DEL selection methods with purified proteins on solid phase, and then we discuss the strategies to realize DEL selections in solution phase. Finally, we focus on the emerging approaches for DELs to interrogate complex biological targets.
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