ArticleJournal of combinatorial chemistry
On-bead screening of combinatorial libraries: reduction of nonspecific binding by decreasing surface ligand density.
Article in Journal of combinatorial chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
- Encoding and display technologies for combinatorial libraries in drug discovery: The coming of age from biology to therapy.Acta pharmaceutica Sinica. B · 2024Review
- Advances in Ultrahigh Throughput Hit Discovery with Tandem Mass Spectrometry Encoded Libraries.Journal of the American Chemical Society · 2023Review
- Mega-High-Throughput Screening Platform for the Discovery of Biologically Relevant Sequence-Defined Non-Natural Polymers.ACS central science · 2022Article
- Automated affinity selection for rapid discovery of peptide binders.Chemical science · 2021Article
- Off-DNA DNA-Encoded Library Affinity Screening.ACS combinatorial science · 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
- Multiplexed Competitive Screening of One-Bead-One-Component Combinatorial Libraries Using a ClonePix 2 Colony Sorter.International journal of molecular sciences · 2019Article
- Protein-Catalyzed Capture Agents.Chemical reviews · 2019Review
- Quantitative mapping of protein-peptide affinity landscapes using spectrally encoded beads.eLife · 2019Article
- Solid-Phase Synthesis of β-Amino Ketones Via DNA-Compatible Organocatalytic Mannich Reactions.ACS combinatorial science · 2018Article
- Cell-permeable bicyclic peptidyl inhibitors against T-cell protein tyrosine phosphatase from a combinatorial library.Organic & biomolecular chemistry · 2017Article
- Screening and identification of mimotopes of the major shrimp allergen tropomyosin using one-bead-one-compound peptide libraries.Cellular & molecular immunology · 2017Article
- Tumor-targeting peptides from combinatorial libraries.Advanced drug delivery reviews · 2017Review
- An efficient strategy to enhance binding affinity and specificity of a known isozyme inhibitor.Organic & biomolecular chemistry · 2016Article
- Peptoid Library Agar Diffusion (PLAD) Assay for the High-Throughput Identification of Antimicrobial Peptoids.ACS combinatorial science · 2016Article
- hνSABR: Photochemical Dose-Response Bead Screening in Droplets.Analytical chemistry · 2016Article
- Discovery of a Direct Ras Inhibitor by Screening a Combinatorial Library of Cell-Permeable Bicyclic Peptides.ACS combinatorial science · 2016Article
- Cell-permeable bicyclic peptide inhibitors against intracellular proteins.Journal of the American Chemical Society · 2014Article
- Utility of redundant combinatorial libraries in distinguishing high and low quality screening hits.ACS combinatorial science · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
On-bead screening of one-bead-one-compound (OBOC) libraries provides a powerful method for the rapid identification of active compounds against molecular or cellular targets. However, on-bead screening is susceptible to interference from nonspecific binding, which results in biased screening data and false positives. In this work, we have found that a major source of nonspecific binding is derived from the high ligand loading on the library beads, which permits a macromolecular target (e.g., a protein) to simultaneously interact with multiple ligands on the bead surface. To circumvent this problem, we have synthesized a phosphotyrosyl (pY)-containing peptide library on spatially segregated TentaGel microbeads, which feature a 10-fold reduced peptide loading on the bead surface but a normal peptide loading in the bead interior. The library was screened against a panel of 10 Src homology 2 (SH2) domains including those of Csk and Fyn kinases and adaptor protein SLAP, and the specific recognition motif(s) was successfully identified for each of the domains. In contrast, when the SH2 domains were screened against a control library that contained unaltered (high) ligand loading at the bead surface, six of them exhibited varying degrees of sequence biases, ranging from minor perturbation in the relative abundance of different sequences to the exclusive selection of false positive sequences that have no measurable affinity to the target protein. These results indicate that reduction of the ligand loading on the bead surface represents a simple, effective strategy to largely eliminate the interference from nonspecific binding, while preserving sufficient amounts of materials in the bead interior for compound identification. This finding should further expand the utility of OBOC libraries in biomedical research.
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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.