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Lookup NU author(s): Cameron TaylorORCiD, Dr Grace RoperORCiD, RHIANNA Young, Professor Mike WaringORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
DNA-encoded libraries (DELs) are established as an effective screening strategy to identify protein ligands and offer a cost-effective means of screening large numbers of compounds. However, the synthesis and utilisation of DELs is implemented by relatively few laboratories. Here, we describe the design and synthesis of a medium-sized DEL through simple amide coupling procedures. We provide details of chemistry and enzymatic steps and demonstrate their effectiveness by synthesising 300k and 3M-member DELs. We demonstrate their integrity through screening against carbonic anhydrase IX and show their chemical diversity through in silico comparison with an established high-throughput screening library. The DELs described can be used as a resource to accelerate hit identification for early-phase drug discovery and are available to the academic community for screening.
Author(s): Taylor CE, Roper G, Young R, Svensson F, Brunschweiger A, Butterworth S, Leach AG, Waring MJ
Publication type: Article
Publication status: Published
Journal: RSC Medicinal Chemistry
Year: 2025
Volume: 16
Issue: 10
Pages: 4774-4780
Print publication date: 01/10/2025
Online publication date: 29/07/2025
Acceptance date: 24/07/2025
Date deposited: 29/07/2025
ISSN (print): 2040-2503
ISSN (electronic): 2040-2511
Publisher: Royal Society of Chemistry
URL: https://doi.org/10.1039/D5MD00350D
DOI: 10.1039/D5MD00350D
Data Access Statement: Full experimental details and data supporting this article are available in the supplementary information.
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