ArticleACS medicinal chemistry letters2021
DNA-Encoded Library Hit Confirmation: Bridging the Gap Between On-DNA and Off-DNA Chemistry.
Article in ACS medicinal chemistry letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Discrete On-DNA Screening: A Frontier for Rapid Hit-to-Lead Optimization Applied to p38α.ACS medicinal chemistry letters · 2026Article
- Assessing the Generalizability of Machine Learning and Physics-Based Methods with DNA-Encoded Libraries.bioRxiv : the preprint server for biology · 2026Article
- Enabling Open Machine Learning of Deoxyribonucleic Acid-Encoded Library Selections to Accelerate the Discovery of Small Molecule Protein Binders.Journal of medicinal chemistry · 2025Article
- Traversing the drug discovery landscape using native mass spectrometry.Current opinion in structural biology · 2025Review
- From DNA-Encoded Library Screening toJournal of medicinal chemistry · 2025Article
- Building Block-Centric Approach to DNA-Encoded Library Design.Journal of chemical information and modeling · 2024Article
- Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications.Beilstein journal of organic chemistry · 2024Article
- Dose-Response Activity-Based DNA-Encoded Library Screening.ACS medicinal chemistry letters · 2023Article
- Accelerating Drug Discovery: Synthesis of Complex Chemotypes via Multicomponent Reactions.ACS medicinal chemistry letters · 2023Review
- Development of the Inverse Sonogashira Reaction for DEL Synthesis.ACS medicinal chemistry letters · 2023Article
- Biomacromolecule-Assisted Screening for Reaction Discovery and Catalyst Optimization.Chemical reviews · 2022Review
- On-DNA Hydroalkylation to Introduce Diverse Bicyclo[1.1.1]pentanes and Abundant Alkyls via Halogen Atom Transfer.Journal of the American Chemical Society · 2022Article
- High-Throughput Binder Confirmation (HTBC).Methods in molecular biology (Clifton, N.J.) · 2022Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA-encoded library (DEL) technology is a powerful platform for hit identification in academia and the pharmaceutical industry. When conducting off-DNA resynthesis hit confirmation after affinity selection, PCR/sequencing, and data analysis, one typically assumes a "one-to-one" relationship between the DNA tag and the chemical structure of the attached small-molecule it encodes. Because library synthesis often yields a mixture, this approximation increases the risk of overlooking positive discoveries and valuable information. To address this issue, we apply a library synthesis "recipe" strategy for on-DNA resynthesis using a cleavable linker, followed by direct affinity selection mass spectrometry (AS-MS) evaluation and identification of binder(s) from the released small-molecule mixture. We validate and showcase this approach employing the receptor-interacting-protein kinase 2 (RIP2) DEL campaign. We also designed and developed two cleavable linkers to enable this method, a photocleavable linker (nitrophenyl-based) and acid-labile linker (tetrahydropyranyl ether). The strategy provides an effective means of hit identification and rapid determination of key active component(s) of the mixture.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.