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Encoded combinatorial chemistry.
Open accessAbstract
The diversity of chemical synthesis and the power of genetics are linked to provide a powerful, versatile method for drug screening. A process of alternating parallel combinatorial synthesis is used to encode individual members of a large library of chemicals with unique nucleotide sequences. After the chemical entity is bound to a target, the genetic tag can be amplified by replication and utilized for enrichment of the bound molecules by serial hybridization to a subset of the library. The nature of the chemical structure bound to the receptor is decoded by sequencing the nucleotide tag.
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“Originally conceived by Brenner and lerner, Dels are built through iterative chemical synthesis in which each small molecule is covalently linked to a unique DNA tag that enables the parallel screening of millions of pooled compounds (Brenner and lerner 1992).”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as Brenner and lerner 1992
Experimental — accuracy not yet measuredIn the citing paper
“Conceptualized by Brenner and Lerner, 170 DNA encoded libraries (DELs) are increasingly being adopted in drug discovery.”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [170]
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“DELs comprise small molecules that are covalently linked to unique DNA sequences that encode, most frequently, their synthetic histories.(2,3) Large collections of DNA-barcoded compounds can be screened in a single experiment by incubating them with an immobilized macromolecular target, washing away nonbinders, and se…”
BackgroundThe generation of molecular diversity
Pavia, M. R., Sawyer, T. K., & Moos, W. H. (1993) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(01)80220-1 · Cited by 115
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“While numerous encoding techniques have been reported [28], including spatial [30], chemical [21,22, 31 ,32], spectrometric”
BackgroundRecent achievements and current trajectories of diversity-oriented synthesis
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[NdI2(thf)5], the First Crystallographically Authenticated Neodymium(II) Complex
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Metadata
- Authors
- Brenner, S., & Lerner, R. A.
- Affiliations
- Scripps Research Institute (US)
- ORCID
- Lerner, R A
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1992-06-15
- Volume
- 89
- Issue
- 12
- Pages
- 5381-5383
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC49295
- OpenAlex
- W2017423606
- Cited by
- 1,014
- References
- 9
- Citations by year
- 2026: 60 · 2025: 77 · 2024: 71 · 2023: 73 · 2022: 87 · 2021: 72 · 2020: 52 · 2019: 55 · 2018: 30 · 2017: 32 · 2016: 25 · 2015: 24 · 2014: 13 · 2013: 9 · 2012: 8
- FWCI
- 8.46
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Keywords
- drug screening, gene tagging, ligand-receptor binding
- MeSH terms
- Amino Acid Sequence, Base Sequence, Molecular Sequence Data, Peptides, Restriction Mapping, Drug Design, Polymerase Chain Reaction, Databases, Factual
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