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库合成:砌块选择、处理和跟踪。

Library Synthesis: Building Block Selection, Handling, and Tracking.

机构信息

Relay Therapeutics, Cambridge, MA, USA.

Encoded Library Technologies/NCE Molecular Discovery, R & D Medicinal Science and Technology, GlaxoSmithKline, Cambridge, MA, USA.

出版信息

Methods Mol Biol. 2022;2541:1-11. doi: 10.1007/978-1-0716-2545-3_1.

DOI:10.1007/978-1-0716-2545-3_1
PMID:36083536
Abstract

Careful selection and manipulation of small molecule building blocks is crucial to the success of a DNA-encoded library. Building block selection impacts the quality of the hits arising out of a selection assay, while proper sample handling and tracking ensure follow-up synthetic work is done with the appropriate synthetic map in mind. In this chapter, possible strategies for building block selection are outlined, as well as best practices for handling and tracking samples to be used for validation and library synthesis.

摘要

对小分子构建块进行仔细的选择和操作对于 DNA 编码文库的成功至关重要。构建块的选择会影响选择测定中产生的命中质量,而正确的样品处理和跟踪可确保后续合成工作是在考虑适当的合成图的情况下进行的。本章概述了构建块选择的可能策略,以及用于验证和文库合成的样品处理和跟踪的最佳实践。

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Library Synthesis: Building Block Selection, Handling, and Tracking.库合成:砌块选择、处理和跟踪。
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本文引用的文献

1
Design and Application of a DNA-Encoded Macrocyclic Peptide Library.DNA编码大环肽库的设计与应用
ACS Chem Biol. 2018 Jan 19;13(1):53-59. doi: 10.1021/acschembio.7b00852. Epub 2017 Dec 4.
2
Analysis of Current DNA Encoded Library Screening Data Indicates Higher False Negative Rates for Numerically Larger Libraries.当前DNA编码文库筛选数据的分析表明,数量较大的文库假阴性率更高。
ACS Comb Sci. 2017 Apr 10;19(4):234-238. doi: 10.1021/acscombsci.7b00023. Epub 2017 Mar 17.
3
DNA-Encoded Library Screening Identifies Benzo[b][1,4]oxazepin-4-ones as Highly Potent and Monoselective Receptor Interacting Protein 1 Kinase Inhibitors.
DNA 编码文库筛选鉴定出苯并[b][1,4]恶嗪-4-酮类化合物为高活性和单选择性受体相互作用蛋白 1 激酶抑制剂。
J Med Chem. 2016 Mar 10;59(5):2163-78. doi: 10.1021/acs.jmedchem.5b01898. Epub 2016 Feb 23.
4
Price-Focused Analysis of Commercially Available Building Blocks for Combinatorial Library Synthesis.用于组合库合成的市售构件的价格聚焦分析。
ACS Comb Sci. 2015 Oct 12;17(10):600-7. doi: 10.1021/acscombsci.5b00063. Epub 2015 Sep 15.
5
Discovery, SAR, and X-ray Binding Mode Study of BCATm Inhibitors from a Novel DNA-Encoded Library.来自新型DNA编码文库的BCATm抑制剂的发现、构效关系及X射线结合模式研究
ACS Med Chem Lett. 2015 Jul 21;6(8):919-24. doi: 10.1021/acsmedchemlett.5b00179. eCollection 2015 Aug 13.
6
An analysis of the attrition of drug candidates from four major pharmaceutical companies.对四大制药公司候选药物淘汰的分析。
Nat Rev Drug Discov. 2015 Jul;14(7):475-86. doi: 10.1038/nrd4609. Epub 2015 Jun 19.
7
Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library.利用化学连接法进行编码文库合成以及从一个拥有3.34亿个成员的文库中发现可溶性环氧化物水解酶抑制剂
Sci Rep. 2015 Jun 10;5:10916. doi: 10.1038/srep10916.
8
Application of encoded library technology (ELT) to a protein-protein interaction target: discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists.编码文库技术(ELT)在蛋白质-蛋白质相互作用靶点中的应用:一类强效整合素淋巴细胞功能相关抗原1(LFA-1)拮抗剂的发现。
Bioorg Med Chem. 2014 Apr 1;22(7):2353-65. doi: 10.1016/j.bmc.2014.01.050. Epub 2014 Feb 7.
9
Discovery of highly potent and selective small molecule ADAMTS-5 inhibitors that inhibit human cartilage degradation via encoded library technology (ELT).通过编码文库技术(ELT)发现高效且选择性的小分子 ADAMTS-5 抑制剂,可抑制人软骨降解。
J Med Chem. 2012 Aug 23;55(16):7061-79. doi: 10.1021/jm300449x. Epub 2012 Aug 14.
10
Probing the links between in vitro potency, ADMET and physicochemical parameters.探究体外效力、ADMET 和理化参数之间的联系。
Nat Rev Drug Discov. 2011 Mar;10(3):197-208. doi: 10.1038/nrd3367.