ArticleAngewandte Chemie (International ed. in English)2022
Multiplexed Small-Molecule-Ligand Binding Assays by Affinity Labeling and DNA Sequence Analysis.
Article in Angewandte Chemie (International ed. in English), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Palladium-Catalyzed Addition of Aryl Halides toJournal of the American Chemical Society · 2024Article
- Recording Binding Information Directly into DNA-Encoded Libraries Using Terminal Deoxynucleotidyl Transferase.Journal of the American Chemical Society · 2023Article
- Facile electrochemical affinity measurements of small and large molecules.RSC advances · 2023Article
- Adsorption Kinetic Model Predicts and Improves Reliability of Electrochemical Serotonin Detection.Methods and protocols · 2023Article
- Selection methods for proximity-dependent enrichment of ligands from DNA-encoded libraries using enzymatic fusion proteins.Chemical science · 2023Article
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Authors and funding
2 authors.
Funding
Abstract
Small-molecule binding assays to target proteins are a core component of drug discovery and development. While a number of assay formats are available, significant drawbacks still remain in cost, sensitivity, and throughput. To improve assays by capitalizing on the power of DNA sequence analysis, we have developed an assay method that combines DNA encoding with split-and-pool sample handling. The approach involves affinity labeling of DNA-linked ligands to a protein target. Critically, the labeling event assesses ligand binding and enables subsequent pooling of several samples. Application of a purifying selection on the pool for protein-labeled DNAs allows detection of ligand binding by quantification of DNA barcodes. We demonstrate the approach in both ligand displacement and direct binding formats and demonstrate its utility in determination of relative ligand affinity, profiling ligand specificity, and high-throughput small-molecule screening.
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