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筛选超大编码化合物库可导致新的蛋白质-配体相互作用和高选择性。

Screening Ultra-Large Encoded Compound Libraries Leads to Novel Protein-Ligand Interactions and High Selectivity.

机构信息

AstraZeneca, Cambridge CB2 0AA, U.K.

X-Chem, Inc., Waltham, Massachusetts 02453, United States.

出版信息

J Med Chem. 2024 Jan 25;67(2):864-884. doi: 10.1021/acs.jmedchem.3c01861. Epub 2024 Jan 10.

DOI:10.1021/acs.jmedchem.3c01861
PMID:38197367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10823476/
Abstract

The DNA-encoded library (DEL) discovery platform has emerged as a powerful technology for hit identification in recent years. It has become one of the major parallel workstreams for small molecule drug discovery along with other strategies such as HTS and data mining. For many researchers working in the DEL field, it has become increasingly evident that many hits and leads discovered via DEL screening bind to target proteins with unique and unprecedented binding modes. This Perspective is our attempt to analyze reports of DEL screening with the purpose of providing a rigorous and useful account of the binding modes observed for DEL-derived ligands with a focus on binding mode novelty.

摘要

近年来，DNA 编码文库（DEL）发现平台已成为一种强大的命中鉴定技术。它已成为小分子药物发现的主要平行工作流程之一，其他策略如高通量筛选和数据挖掘也是如此。对于许多从事 DEL 领域研究的研究人员来说，越来越明显的是，通过 DEL 筛选发现的许多命中和先导化合物与靶蛋白结合的方式独特且前所未有的。本观点分析了 DEL 筛选报告，旨在为 DEL 衍生配体的观察到的结合模式提供严格而有用的描述，重点是结合模式的新颖性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8932/10823476/686257bcbb2c/jm3c01861_0013.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8932/10823476/e82b219ea595/jm3c01861_0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8932/10823476/002545158362/jm3c01861_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8932/10823476/23f07ded1a9d/jm3c01861_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8932/10823476/7014aa27ecc8/jm3c01861_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8932/10823476/af47c0dc3d23/jm3c01861_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8932/10823476/9d00f8c97df8/jm3c01861_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8932/10823476/07b34d46a20d/jm3c01861_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8932/10823476/c05840004ec7/jm3c01861_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8932/10823476/b4dce97c24f9/jm3c01861_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8932/10823476/b3de04ba4135/jm3c01861_0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8932/10823476/686257bcbb2c/jm3c01861_0013.jpg

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