ArticleACS combinatorial science2014
Utility of redundant combinatorial libraries in distinguishing high and low quality screening hits.
Article in ACS combinatorial science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- RNA-Focused DNA-Encoded Library Construction, Screening, and Integration of Docking Identify Bioactive Ligands of Pathogenic r(GbioRxiv : the preprint server for biology · 2025Article
- Building Block-Based Binding Predictions for DNA-Encoded Libraries.Journal of chemical information and modeling · 2023Article
- Synthesis and Screening of a DNA-Encoded Library of Non-Peptidic Macrocycles.Angewandte Chemie (International ed. in English) · 2022Article
- High-Throughput Quality Control Assay for the Solid-Phase Synthesis of DNA-Encoded Libraries of Macrocycles*.Angewandte Chemie (International ed. in English) · 2021Article
- Methods for the discovery of small molecules to monitor and perturb the activity of the human proteasome.Future medicinal chemistry · 2021Review
- Structural characterization of a peptoid-inspired conformationally constrained oligomer (PICCO) bound to streptavidin.Chemical communications (Cambridge, England) · 2020Article
- Beyond protein binding: recent advances in screening DNA-encoded libraries.Chemical communications (Cambridge, England) · 2019Review
- Developments with bead-based screening for novel drug discovery.Expert opinion on drug discovery · 2019Article
- Chemical composition of DNA-encoded libraries, past present and future.Organic & biomolecular chemistry · 2019Review
- Activity-Based DNA-Encoded Library Screening.ACS combinatorial science · 2019Article
- Article
- Xenoprotein engineering via synthetic libraries.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Solid-Phase Synthesis of β-Hydroxy Ketones Via DNA-Compatible Organocatalytic Aldol Reactions.ACS combinatorial science · 2018Article
- Solid-Phase Synthesis of β-Amino Ketones Via DNA-Compatible Organocatalytic Mannich Reactions.ACS combinatorial science · 2018Article
- Library Design-Facilitated High-Throughput Sequencing of Synthetic Peptide Libraries.ACS combinatorial science · 2017Article
- Poisson Statistics of Combinatorial Library Sampling Predict False Discovery Rates of Screening.ACS combinatorial science · 2017Article
- Asymmetric synthesis of vinylogous β-amino acids and their incorporation into mixed backbone oligomers.Organic & biomolecular chemistry · 2017Article
- Discovery of Peptidomimetic Ligands of EED as Allosteric Inhibitors of PRC2.ACS combinatorial science · 2017Article
- An Integrated Microfluidic Processor for DNA-Encoded Combinatorial Library Functional Screening.ACS combinatorial science · 2017Article
- Tumor-targeting peptides from combinatorial libraries.Advanced drug delivery reviews · 2017Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Large one-bead one-compound (OBOC) combinatorial libraries can be constructed relatively easily by solid-phase split and pool synthesis. The use of resins with hydrophilic surfaces, such as TentaGel, allows the beads to be used directly in screens for compounds that bind selectively to labeled proteins, nucleic acids, or other biomolecules. However, we have found that this method, while useful, has a high false positive rate. In other words, beads that are scored as hits often display compounds that prove to be poor ligands for the target of interest when they are resynthesized and carried through validation trials. This results in a significant waste of time and resources in cases where putative hits cannot be validated without resynthesis. Here, we report that this problem can be largely eliminated through the use of redundant OBOC libraries, where more than one bead displaying the same compound is present in the screen. We show that compounds isolated more than once are likely to be high quality ligands for the target of interest, whereas compounds isolated only once have a much higher likelihood of being poor ligands. While the use of redundant libraries does limit the number of unique compounds that can be screened at one time in this format, the overall savings in time, effort, and materials makes this a more efficient route to the isolation of useful ligands for biomolecules.
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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.