The DOI matches its Crossref record; 97 of the 97 references it cites were found in a registry or an index.
DNA-Encoded Chemical Libraries: A Selection System Based on Endowing Organic Compounds with Amplifiable Information
Open accessAbstract
The discovery of organic ligands that bind specifically to proteins is a central problem in chemistry, biology, and the biomedical sciences. The encoding of individual organic molecules with distinctive DNA tags, serving as amplifiable identification bar codes, allows the construction and screening of combinatorial libraries of unprecedented size, thus facilitating the discovery of ligands to many different protein targets. Fundamentally, one links powers of genetics and chemical synthesis. After the initial description of DNA-encoded chemical libraries in 1992, several experimental embodiments of the technology have been reduced to practice. This review provides a historical account of important milestones in the development of DNA-encoded chemical libraries, a survey of relevant ongoing research activities, and a glimpse into the future.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“DNA-encoded libraries (DELs), which have the potential to sample vast chemical space in the span of one or more closely related experiments (>109 compounds) 133 .”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [133]
Experimental — accuracy not yet measuredIn the citing paper
“More recently, DNA-econded chemical libraries have made possible synthesis and testing of millions of compounds165 and many big pharma companies have embraced this approach.”
From QSAR without borders (2020) · cites this paper as [165]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Continuous cultures of fused cells secreting antibody of predefined specificity
Köhler, G., & Milstein, C. (1975) · Nature · doi:10.1038/256495a0 · Cited by 17,200
Smith, G. P. (1985) · Science · doi:10.1126/science.4001944 · Cited by 4,143
Rapid generation of functional human IgG antibodies derived from Fab-on-phage display libraries
Jostock, T., Vanhove, M., Brepoels, E., van Gool, R., Daukandt, M., Wehnert, A., van Hegelsom, R., Dransfield, D., Sexton, D., Devlin, M., et al. (2004) · Journal of Immunological Methods · doi:10.1016/j.jim.2004.03.014 · Cited by 2,572
Phage antibodies: filamentous phage displaying antibody variable domains
McCafferty, J., Griffiths, A. D., Winter, G. P., & Chiswell, D. J. (1990) · Nature · doi:10.1038/348552a0 · Cited by 2,427
Marks, J. D., Hoogenboom, H. R., Bonnert, T. P., McCafferty, J., Griffiths, A. D., & Winter, G. P. (1991) · Journal of Molecular Biology · doi:10.1016/0022-2836(91)90498-u · Cited by 1,605
Sapsford, K. E., Algar, W. R., Berti, L., Gemmill, K. B., Casey, B. J., Oh, E., Stewart, M. H., & Medintz, I. L. (2013) · Chemical Reviews · doi:10.1021/cr300143v · Cited by 1,470
Encoded combinatorial chemistry.
Brenner, S., & Lerner, R. A. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.12.5381 · Cited by 1,014 · cited 1×
“) together with Sidney Brenner postulated that it should be possible to “encode” chemistry with DNA (26).”
BackgroundSelf-citationTwenty years on: the impact of fragments on drug discovery
Erlanson, D. A., Fesik, S. W., Hubbard, R. E., Jahnke, W., & Jhoti, H. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.109 · Cited by 1,000
Isolation of high affinity human antibodies directly from large synthetic repertoires.
Griffiths, A. D., Williams, S. C., Hartley, O., Tomlinson, I. M., Waterhouse, P. M., Crosby, W. L., Kontermann, R. E., Jones, P. T., Low, N. M., & Allison, T. J. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06626.x · Cited by 962
Winter, G. P., & Milstein, C. (1991) · Nature · doi:10.1038/349293a0 · Cited by 958
Research works printed but not linked: 3
- Stark JL, 2012, Top. Curr. Chem., 326, 1
- Neri D, 2002, Encoded self-assembling chemical libraries
- Li Y, Nat. Chem, 10, 2018
Cited by
Sorted by citations
Items 301–378 of 378
On-DNA Deoxygenative C(sp 2 )–C(sp 3 ) Coupling Facilitated by Surfactant–DNA (Surf-DNA) Workflow
Chheda, P. R., Finis, D. S., Simmons, N., & Shi, Z. (2025) · Organic Letters · doi:10.1021/acs.orglett.5c03424 · Cited by 2
Biocompatible decarboxylative coupling enabled by N-hydroxynaphthalimide esters
Liao, H., Su, Z., Zhang, J., Liu, S., Fan, M.-J., Wang, S., Sun, F., Jiao, W., Li, L., Zhu, H., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65244-7 · Cited by 2
Affinity selection mass spectrometry (AS-MS) as a tool to accelerate drug discovery efforts
Pandey, S., Samain, F., Nacham, O., Williams, J. D., & Elsen, N. L. (2026) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2026.2622373 · Cited by 3
Rapid Discovery of CD38 Inhibitor via DNA-Encoded Natural Product Library Screening
Shi, X., Liang, Z., Meng, W., Yang, G., & Yan, L. (2026) · Molecules · doi:10.3390/molecules31050864 · Cited by 2
Drug discovery: Chaos can be your friend or your enemy
Miller, S. M., Moos, W. H., Munk, B. H., Munk, S. A., Hart, C. P., & Spellmeyer, D. C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-824304-6.00012-2 · Cited by 3
Motohashi, Y., Moritani, S., Nishihara, T., & Tanabe, K. (2023) · ChemistrySelect · doi:10.1002/slct.202302662 · Cited by 2
Motohashi, Y., Nishihara, T., & Tanabe, K. (2023) · Chemistry Letters · doi:10.1246/cl.230263 · Cited by 2
Nishihara, T., Motohashi, Y., Mio, R., Sugawara, M., & Tanabe, K. (2024) · Chemical Communications · doi:10.1039/d4cc01470g · Cited by 2
Surf–DNA-Enabled DNA-Encoded Library-Compatible Amino Radical Transfer C(sp2)–C(sp3) Coupling
Finis, D. S., Simmons, N., Shi, Z., & Chheda, P. R. (2025) · Organic Letters · doi:10.1021/acs.orglett.5c02769 · Cited by 2
2nd PSL Chemical Biology Symposium (2019): At the Crossroads of Chemistry and Biology
Lucchino, M., Billet, A., Versini, A., Bavireddi, H., Dasari, B., Debieu, S., Colombeau, L., Cañeque, T., Wagner, A., Masson, G., et al. (2019) · ChemBioChem · doi:10.1002/cbic.201900092 · Cited by 2
Towards a templated reaction that translates RNA in cells into a proaptotic peptide‐PNA conjugate
Altrichter, Y., Dib, P. B., Kuznia, C., & Seitz, O. (2023) · Journal of Peptide Science · doi:10.1002/psc.3477 · Cited by 2
Harnessing in Silico Technologies to Develop and Augment Second-Generation Cell-Based Therapies
Ruff, C. A., & Vertès, A. A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-812034-7.00007-8 · Cited by 2
Gui, Y., Hou, R., Huang, Y., Zhou, Y., Liu, S., Meng, L., Li, Y., Lam, F. S., Wong, C. S., Yin, C. T., et al. (2024) · ChemRxiv · doi:10.26434/chemrxiv-2024-3mrz3 · Cited by 1
Recent Advances in the Use and Impact of DNA-Encoded Libraries in Drug Discovery
Dombrowski, A. W., & Samain, F. (2026) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.6c00047 · Cited by 2
Puglioli, S., Fabbri, M., Comacchio, C., Alvigini, L., Luca, R. D., Oehler, S., Gilardoni, E., Bassi, G., Cazzamalli, S., Neri, D., et al. (2024) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.4c00233 · Cited by 1
Self-citationResearch progress of DNA barcoding in precision medicine and molecular diagnosis- A review
Zhou, Z., Mao, D., Chen, G., Feng, C., & Zhu, X. (2025) · Analytica Chimica Acta · doi:10.1016/j.aca.2025.344492 · Cited by 1
Park, J., Lim, H., Lee, Y., Kim, T., Song, H., Lee, S., Heo, Y., Kim, J. S., Namkung, W., & Han, G. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.109285 · Cited by 1
Zhang, Y., Mantell, M. A., Summerfield, J. D., & Marcaurelle, L. A. (2026) · Organic Letters · doi:10.1021/acs.orglett.6c01468 · Cited by 1
Schaub, D., Lessing, A., Meyer, F., Stockinger, P., Estévez‐Gay, M., Eichenberger, M., von Haugwitz, G., Gloger, A., Scheuermann, J., & Buller, R. (2026) · Nature Catalysis · doi:10.1038/s41929-026-01576-x · Cited by 3
Screening and biophysics in small molecule discovery
Wilson, C. G. M., & Arkin, M. R. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818349-6.00005-4 · Cited by 1
Immunoglobulin Go: Synergy of Combinatorics for Catalysis
Smirnov, I. V., Belogurov, A. A., Golovin, A. V., Stepanov, A. V., Zhang, H., Blackburn, G. M., & Gabibov, A. G. (2023) · Israel Journal of Chemistry · doi:10.1002/ijch.202300078 · Cited by 1
Asymmetry of Dual-Display DNA-Encoded Chemical Libraries
Plais, L., Trachsel, L., & Scheuermann, J. (2024) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.3c00559 · Cited by 1
Translation of Deoxyribonucleic Acid into Synthetic Alpha Helical Peptides for Darwinian Evolution
Dockerill, M., Sabale, P. M., Russo, F., Barluenga, S., & Winssinger, N. (2024) · JACS Au · doi:10.1021/jacsau.4c00738 · Cited by 1
Yadav, P., Asa, T. A., Cebeci, M., Choi, M.-G., & Seo, Y. J. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c01151 · Cited by 1
Nonlinear manipulation and analysis of large DNA datasets
Cui, M., Zhao, X., Reddavide, F. V., Gaillez, M. P., Heiden, S., Mannocci, L., Thompson, M., & Zhang, Y. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac672 · Cited by 2
High-Throughput Binder Confirmation Using Affinity Selection Mass Spectrometry
Shi, E. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2545-3_25 · Cited by 1
Chemical Approaches for Beta-cell Biology
Vetere, A., Parekh, V. S., Modell, A. E., Shoba, V. M., Choudhary, A., & Wagner, B. K. (2022) · Royal Society of Chemistry eBooks · doi:10.1039/9781839165498-00001 · Cited by 1
Ein Fest der Wissenschaft inmitten der Natur: Die 54. Bürgenstock‐Konferenz
Baráth, E., & Mejía, E. (2019) · Angewandte Chemie · doi:10.1002/ange.201906781
A Celebration of Science amidst Nature: The 54th Bürgenstock Conference
Baráth, E., & Mejía, E. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201906781
PNA-Encoded Synthesis (PES) and DNA Display of Small Molecule Libraries
Saarbach, J., Gajić, J., Barluenga, S., & Winssinger, N. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0243-0_7
Paul Greengard: A persistent desire to comprehend the brain, and also to fix it
Flajolet, M., Nguyen, T. L., Siripuram, V. K., & Sunkari, Y. K. (2020) · Advances in pharmacology · doi:10.1016/bs.apha.2020.09.008
Chemisch stabilisierte DNA‐Codes für DNA‐kodierte Chemie
Potowski, M., Kunig, V. B. K., Eberlein, L., Vakalopoulos, A., Kast, S. M., & Brunschweiger, A. (2021) · Angewandte Chemie · doi:10.1002/ange.202104348
Faculty Opinions recommendation of How We Think about Targeting RNA with Small Molecules.
Lowe, J. A., III (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.737636298.793572902
Synthesis and Screening of A DNA-Encoded Library of Non-Peptidic MacrocyclesPreprint
Koesema, E., Roy, A. C., Paciaroni, N. G., & Kodadek, T. J. (2020) · ChemRxiv · doi:10.26434/chemrxiv.13490151
DNA‐ENCODED CHEMICAL LIBRARIES USED FOR DRUG DISCOVERY
Zhao, G., Yang, S., Li, X., & Li, Y. (2022) · Wiley eBooks · doi:10.1002/9781119692799.ch8
Foreword to the second edition
Selick, H. E. “. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-824304-6.00024-9
Kodadek, T. J. (2023) · Angewandte Chemie · doi:10.1002/ange.202316726
Scheuermann, J. (2024) · Haug Verlag in Georg Thieme Verlag KG eBooks · doi:10.1055/sos-sd-241-00255
3.2.2.1 Encoded Self-Assembling (Dynamic) Chemical Libraries
Prati, L., Lucaroni, L., Cazzamalli, S., Neri, D., & Oehler, S. (2024) · Haug Verlag in Georg Thieme Verlag KG eBooks · doi:10.1055/sos-sd-241-00223
Self-citationSelection of Leptin Surrogates by a General Phenotypic Screening Method for Receptor Agonists
Wang, T., Chen, X., Yang, G., & Shi, X. (2024) · Biomolecules · doi:10.3390/biom14040457
CNS Biased Agonism and the Promise of Targeting Drugs Beyond Receptors to Cellular Pathways
Melnick, L. M. (2024) · Springer eBooks · doi:10.1007/978-3-031-61992-2_9
Gui, Y., Hou, R., Huang, Y., Zhou, Y., Liu, S., Meng, L., Li, Y., Lam, F. S., Ding, R., Cao, Y. W., et al. (2025) · Angewandte Chemie · doi:10.1002/ange.202421172
Application of DELs for E3 Ligase Ligand Discovery and Targeted Protein Degradation
Malone, M. L., Sanchez, N. A., Hu, S. L., & Phelps, C. B. (2025) · Royal Society of Chemistry eBooks · doi:10.1039/9781788016032-00134
Native Massenspektrometrie erleichtert die Hit‐Validierung in der DNA‐Encoded Library Technologie
Bittner, P., Gloger, A., Keller, M., Oehler, S., Lessing, A., Zhang, Q., Ma, Z., Su, W., Satz, A. L., Kuai, L., et al. (2025) · Angewandte Chemie · doi:10.1002/ange.202504470
Dong, K., Meng, X., Diao, H., Qi, B., Chen, Z., Ma, W., Zhang, Y., Yang, M., Zhao, J., & Liu, L. (2025) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c00816
CIMT 2025: Report on the 22 nd Annual Meeting of the Association for Cancer Immunotherapy
Dahl, L., Kiefer, J., Klein, L., Linkenbach, S.-C., Muralidharan, A. M., Peter, M., Tagscherer, N., & Beck, J. D. (2025) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2025.2563962
Nishihara, T., Sugawara, M., Mio, R., Motohashi, Y., & Tanabe, K. (2026) · Chemical & Biomedical Imaging · doi:10.1021/cbmi.5c00226
Huang, Y., Tan, X., Li, X., Xiong, F., & Yiu, S. (2026) · Bioinformatics · doi:10.1093/bioinformatics/btag001
A Novel Method for Normalizing Data from DNA-Encoded Library SelectionsPreprint
Lengyel‐Zhand, Z., Jiang, Z., Montgomery, J. I., Zhu, H., Riccardi, K. A., Corpina, R. A., Burchett, W., Abdelmessih, M., Stanton, R. V., Craig, T. K., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.20.700605
Modern Molecular Biology: Tools, Applications, and the Power of Gene Cloning
Kumar, S., Chuangsangi, L., Mohanta, G. C., & Pandey, S. K. (2026) · Springer eBooks · doi:10.1007/978-981-95-5378-5_7
Microfluidic Agarose µ -Droplets for DNA-Encoded Chemical Library ScreeningPreprint
Kim, Y., Kim, H., Hong, J., Kang, M., 배재영, Ko, S., Kim, M., Koh, B., Kim, H., Shim, S., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.15.706034
Toward the chemoenzymatic synthesis of DNA-encoded libraries
Schaub, D., Lessing, A., von Haugwitz, G., Meyer, F., Scheuermann, J., & Buller, R. (2026) · Zürcher Hochschule für Angewandte Wissenschaften digital collection (Zurich University of Applied Sciences) · doi:10.21256/zhaw-35744
High-Throughput Binding Kinetic Measurements of DNA-Encoded Library-Derived Hits By Focal Molography
Favalli, N., Velti, C., Campari, L., Heuberger, L., Fabbri, M., Müller, M., Puglioli, S., Cazzamalli, S., Neri, D., Frutiger, A., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c01097
Self-citationSynthesis of DNA-Encoded Libraries by Tryptophan-Selective Bioconjugation
Malawska, K., Suzuki, M., Sasaki, J., Koshimizu, M., Kaitoh, K., Miyachi, H., & Kanai, M. (2026) · Organic Letters · doi:10.1021/acs.orglett.6c02201
Oppewal, T. R., & Mayer, C. (2026) · Chemistry - A European Journal · doi:10.1002/chem.71408
Synthesis of Large PNA-Encoded Chemical Libraries via Mismatch-Resistant PNA/DNA Hybridization
Park, J. H., Kim, J., Seo, C. D., Wang, H. M., Lee, Y., & Lim, H. (2026) · Organic Letters · doi:10.1021/acs.orglett.6c02366
Schaub, D., Lessing, A., Meyer, F., Stockinger, P., Estévez‐Gay, M., Eichenberger, M., von Haugwitz, G., Gloger, A., Scheuermann, J., & Buller, R. (2026) · Zürcher Hochschule für Angewandte Wissenschaften digital collection (Zurich University of Applied Sciences) · doi:10.21256/zhaw-37088
Dong, J., Li, B., Fu, C., & Kodadek, T. J. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.6c07205
PhenoDEL: A Novel Screening Strategy Based on Intracellular Protein Degradation Activity
Onda, Y., Ochi, Y., Araki, T., Kageoka, M., Takeda, S., Yamada, K., Ueda, T., Ohno, K., Tanaka, M., Sakai, D., et al. (2026) · ACS Chemical Biology · doi:10.1021/acschembio.6c00234 · Cited by 4
Xia, Z.-M., Wei, H.-M., Xue, J.-H., Sun, Y.-N., Wan, X.-C., Hua-Rong, T. O. N. G., Zhou, L., Shi, P., Fang, G., & Tian, C. (2026) · Chemical Science · doi:10.1039/d6sc03710k
Koshimizu, M., Suzuki, M., Miya, S., & Miyachi, H. (2026) · Organic Chemistry Frontiers · doi:10.1039/d6qo00903d
Cao, H., He, M., Ma, N., Hsieh, C., Yao, X., de la Fuente‐Núñez, C., Gu, C., & Heng, P. A. (2026) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2026.103565
Systematic Evaluation of Washing Conditions to Preserve Low Affinity Binders in DEL Selections
Fabbri, M., Campari, L., Puglioli, S., Alvigini, L., Migliorini, F., Cazzamalli, S., Neri, D., & Favalli, N. (2026) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.6c00428
Self-citationDNA-scaffolded catalysis for aliphatic alcohol oxidation in DEL synthesis
Hartman, E. M., & Martell, J. D. (2026) · Chemical Science · doi:10.1039/d6sc05041g
Brennecke, B., Plais, L., Hornsperger, B., Binder, M., Bartelmus, C., Bürkler, M., O’Hara, F., Kroll, C., Tsuchiya, S., Koçer, B., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c01872
BindingDB Entry 50013495: Dual Bcl-X
BindingDB (2022) · UC San Diego · doi:10.7270/q2t157dk
BindingDB (2022) · UC San Diego · doi:10.7270/q2k0780v
BindingDB (2022) · UC San Diego · doi:10.7270/q2h135tk
Metadata
- Authors
- Neri, D., & Lerner, R. A.
- Affiliations
- ETH Zurich (CH)
- Scripps Research Institute (US)
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2018-06-20
- Volume
- 87
- Issue
- 1
- Pages
- 479-502
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- PMC
- PMC6080696
- OpenAlex
- W2782995788
- Cited by
- 364
- References
- 97
- Citations by year
- 2026: 26 · 2025: 32 · 2024: 27 · 2023: 34 · 2022: 42 · 2021: 63 · 2020: 81 · 2019: 46 · 2018: 13
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030B_163479/1, 163479, 160699)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Keywords
- DNA-encoded libraries, DNA barcoding, combinatorial libraries, protein-ligand binding, ligand discovery, library screening, molecular identification
- MeSH terms
- Animals, Humans, Ligands, Gene Library, Peptide Library, Combinatorial Chemistry Techniques, Small Molecule Libraries, Drug Discovery
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
