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DNA编码动态文库的最新进展。

Recent advances in DNA-encoded dynamic libraries.

作者信息

Shi Bingbing, Zhou Yu, Li Xiaoyu

机构信息

Department of Biochemistry and Molecular Biology, College of Basic Medicine, Jining Medical University Jining Shandong 272067 P. R. China.

Department of Chemistry and State Key Laboratory of Synthetic Chemistry, The University of Hong Kong Pokfulam Road Hong Kong SAR China

出版信息

RSC Chem Biol. 2022 Feb 17;3(4):407-419. doi: 10.1039/d2cb00007e. eCollection 2022 Apr 6.

DOI:10.1039/d2cb00007e
PMID:35441147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8985084/
Abstract

The DNA-encoded chemical library (DEL) has emerged as a powerful technology platform in drug discovery and is also gaining momentum in academic research. The rapid development of DNA-/DEL-compatible chemistries has greatly expanded the chemical space accessible to DELs. DEL technology has been widely adopted in the pharmaceutical industry and a number of clinical drug candidates have been identified from DEL selections. Recent innovations have combined DELs with other legacy and emerging techniques. Among them, the DNA-encoded dynamic library (DEDL) introduces DNA encoding into the classic dynamic combinatorial libraries (DCLs) and also integrates the principle of fragment-based drug discovery (FBDD), making DEDL a novel approach with distinct features from static DELs. In this Review, we provide a summary of the recently developed DEDL methods and their applications. Future developments in DEDLs are expected to extend the application scope of DELs to complex biological systems with unique ligand-discovery capabilities.

摘要

DNA编码化学文库(DEL)已成为药物发现领域强大的技术平台,在学术研究中也日益受到关注。与DNA/DEL兼容的化学方法的迅速发展极大地扩展了DEL可触及的化学空间。DEL技术已在制药行业广泛应用,并且从DEL筛选中已鉴定出许多临床候选药物。最近的创新将DEL与其他传统和新兴技术相结合。其中,DNA编码动态文库(DEDL)将DNA编码引入经典动态组合文库(DCL),还整合了基于片段的药物发现(FBDD)原理,使DEDL成为一种具有别于静态DEL独特特征的新方法。在本综述中,我们总结了最近开发的DEDL方法及其应用。预计DEDL的未来发展将把DEL的应用范围扩展到具有独特配体发现能力的复杂生物系统。

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A mating mechanism to generate diversity for the Darwinian selection of DNA-encoded synthetic molecules.一种产生多样性的交配机制,用于对 DNA 编码的合成分子进行达尔文选择。
Nat Chem. 2022 Feb;14(2):141-152. doi: 10.1038/s41557-021-00829-5. Epub 2021 Dec 6.
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Modular assembly and encoding strategies for dual-display DNA-encoded chemical libraries.用于双显示 DNA 编码化学库的模块化组装和编码策略。
Chem Commun (Camb). 2021 Nov 19;57(92):12289-12292. doi: 10.1039/d1cc04306d.
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Acc Chem Res. 2021 Sep 7;54(17):3491-3503. doi: 10.1021/acs.accounts.1c00375. Epub 2021 Aug 24.
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DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 M inhibitors.DNA 编码化学技术可快速获得 SARS-CoV-2 M 抑制剂。
Proc Natl Acad Sci U S A. 2021 Sep 7;118(36). doi: 10.1073/pnas.2111172118.
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Bioorg Med Chem. 2021 Sep 1;45:116328. doi: 10.1016/j.bmc.2021.116328. Epub 2021 Jul 25.
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