ArticleBioorganic & medicinal chemistry letters2018
Screening one bead one compound libraries against serum using a flow cytometer: Determination of the minimum antibody concentration required for ligand discovery.
Article in Bioorganic & medicinal chemistry letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 19 citations in OpenAlex.
- Synthesis and Screening of a DNA-Encoded Library of Non-Peptidic Macrocycles.Angewandte Chemie (International ed. in English) · 2022Article
- Structural characterization of a peptoid-inspired conformationally constrained oligomer (PICCO) bound to streptavidin.Chemical communications (Cambridge, England) · 2020Article
- Evolving a Peptide: Library Platforms and Diversification Strategies.International journal of molecular sciences · 2019Review
- 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
- Efficient Screening of Combinatorial Peptide Libraries by Spatially Ordered Beads Immobilized on Conventional Glass Slides.High-throughput · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
One bead one compound (OBOC) libraries can be screened against serum samples to identify ligands to antibodies in this mixture. In this protocol, hit beads are identified by staining with a fluorescent labeled secondary antibody. When screens are conducted against two different sets of serum, antibodies, and ligands to them, can be discovered that distinguish the two populations. The application of DNA-encoding technology to OBOC libraries has allowed the use of 10 µm beads for library preparation and screening, which pass through a standard flow cytometer, allowing the fluorescent hit beads to be separated from beads displaying non-ligands easily. An important issue in using this approach for the discovery of antibody biomarkers is its analytical sensitivity. In other words, how abundant must an IgG be to allow it to be pulled out of serum in an unbiased screen using a flow cytometer? We report here a model study in which monoclonal antibodies with known ligands of varying affinities are doped into serum. We find that for antibody ligands typical of what one isolates from an unbiased combinatorial library, the target antibody must be present at 10-50 nM. True antigens, which bind with significantly higher affinity, can detect much less abundant serum antibodies.
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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.