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Issue 89, 2019
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Beyond protein binding: recent advances in screening DNA-encoded libraries

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Abstract

DNA-encoded library (DEL) screening has emerged as an important method for early stage drug and probe molecule discovery. The vast majority of screens using DELs have been relatively simple binding assays. The library is incubated with a target molecule, which is almost always a protein, and the DNAs that remain associated with the target after thorough washing are amplified and deep sequenced to reveal the chemical structures of the ligands they encode. Recently however, a number of different screening formats have been introduced that demand more than simple binding. These include a format that demands hits exhibit high selectivity for target vs. off-targets, a protocol to screen for enzyme inhibitors and another to identify organocatalysts in a DEL. These and other novel assay formats are reviewed in this article. We also consider some of the most significant remaining challenges in DEL assay development.

Graphical abstract: Beyond protein binding: recent advances in screening DNA-encoded libraries

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Publication details

The article was received on 12 Aug 2019, accepted on 14 Oct 2019 and first published on 21 Oct 2019


Article type: Feature Article
DOI: 10.1039/C9CC06256D
Chem. Commun., 2019,55, 13330-13341

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    Beyond protein binding: recent advances in screening DNA-encoded libraries

    T. Kodadek, N. G. Paciaroni, M. Balzarini and P. Dickson, Chem. Commun., 2019, 55, 13330
    DOI: 10.1039/C9CC06256D

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