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DNA 编码文库筛选数据的分析:合成分子的选择。

Analysis of DNA-Encoded Library Screening Data: Selection of Molecules for Synthesis.

机构信息

WuXi AppTec, Planegg, Germany.

出版信息

Methods Mol Biol. 2022;2541:195-205. doi: 10.1007/978-1-0716-2545-3_23.

DOI:10.1007/978-1-0716-2545-3_23
PMID:36083558
Abstract

DNA-encoded library (DEL) screens are used to discover novel chemical matter capable of modulating the activity of pharmaceutically interesting protein targets. DEL selections are accomplished by immobilizing a target protein on a resin and capturing library molecules that bind to the target. The barcodes of the captured library molecules are then amplified and sequenced. This chapter outlines simple methods for visualizing the resulting screening data (using free open-source software), such that enriched molecules can be selected for synthesis and follow-up activity confirmation. Measures of enrichment and the concept of sub-libraries are also illustrated.

摘要

DNA 编码文库 (DEL) 筛选用于发现能够调节有药用价值的蛋白质靶标活性的新型化学物质。DEL 选择是通过将靶蛋白固定在树脂上并捕获与靶标结合的文库分子来完成的。然后对捕获的文库分子的条形码进行扩增和测序。本章概述了可视化筛选结果数据的简单方法(使用免费的开源软件),以便选择富集的分子进行合成和后续活性确认。还说明了富集的度量和子文库的概念。

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本文引用的文献

1
Denoising DNA Encoded Library Screens with Sparse Learning.基于稀疏学习的 DNA 编码文库筛选降噪。
ACS Comb Sci. 2020 Aug 10;22(8):410-421. doi: 10.1021/acscombsci.0c00007. Epub 2020 Jun 26.
2
Quantitative Comparison of Enrichment from DNA-Encoded Chemical Library Selections.DNA 编码化学库筛选的富集度定量比较。
ACS Comb Sci. 2019 Feb 11;21(2):75-82. doi: 10.1021/acscombsci.8b00116. Epub 2019 Jan 23.
3
What Do You Get from DNA-Encoded Libraries?你能从DNA编码文库中获得什么?
ACS Med Chem Lett. 2018 Apr 17;9(5):408-410. doi: 10.1021/acsmedchemlett.8b00128. eCollection 2018 May 10.
4
DNA-encoded chemistry: enabling the deeper sampling of chemical space.DNA 编码化学:实现更深入的化学空间采样。
Nat Rev Drug Discov. 2017 Feb;16(2):131-147. doi: 10.1038/nrd.2016.213. Epub 2016 Dec 9.
5
Simulated Screens of DNA Encoded Libraries: The Potential Influence of Chemical Synthesis Fidelity on Interpretation of Structure-Activity Relationships.DNA编码文库的模拟筛选:化学合成保真度对构效关系解读的潜在影响。
ACS Comb Sci. 2016 Jul 11;18(7):415-24. doi: 10.1021/acscombsci.6b00001. Epub 2016 May 13.
6
Automated screening for small organic ligands using DNA-encoded chemical libraries.使用DNA编码化学文库对小分子有机配体进行自动化筛选。
Nat Protoc. 2016 Apr;11(4):764-80. doi: 10.1038/nprot.2016.039. Epub 2016 Mar 17.
7
DNA Encoded Library Selections and Insights Provided by Computational Simulations.DNA编码文库筛选及计算模拟提供的见解
ACS Chem Biol. 2015 Oct 16;10(10):2237-45. doi: 10.1021/acschembio.5b00378. Epub 2015 Jul 27.
8
DataWarrior: an open-source program for chemistry aware data visualization and analysis.DataWarrior:一款用于化学感知数据可视化与分析的开源程序。
J Chem Inf Model. 2015 Feb 23;55(2):460-73. doi: 10.1021/ci500588j. Epub 2015 Feb 2.
9
Design, synthesis and selection of DNA-encoded small-molecule libraries.DNA编码小分子文库的设计、合成与筛选
Nat Chem Biol. 2009 Sep;5(9):647-54. doi: 10.1038/nchembio.211. Epub 2009 Aug 2.