Fidelity by design: Yoctoreactor and binder trap enrichment for small-molecule DNA-encoded libraries and drug discovery

Current Opinion in Chemical Biology
Peter BlakskjaerNils J V Hansen

Abstract

DNA-encoded small-molecule library (DEL) technology allows vast drug-like small molecule libraries to be efficiently synthesized in a combinatorial fashion and screened in a single tube method for binding, with an assay readout empowered by advances in next generation sequencing technology. This approach has increasingly been applied as a viable technology for the identification of small-molecule modulators to protein targets and as precursors to drugs in the past decade. Several strategies for producing and for screening DELs have been devised by both academic and industrial institutions. This review highlights some of the most significant and recent strategies along with important results. A special focus on the production of high fidelity DEL technologies with the ability to eliminate screening noise and false positives is included: using a DNA junction called the Yoctoreactor, building blocks (BBs) are spatially confined at the center of the junction facilitating both the chemical reaction between BBs and encoding of the synthetic route. A screening method, known as binder trap enrichment, permits DELs to be screened robustly in a homogeneous manner delivering clean data sets and potent hits for even the most challenging ta...Continue Reading

References

Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S Brenner, R A Lerner
Jul 13, 2001·Journal of the American Chemical Society·Z J Gartner, D R Liu
May 17, 2003·Nature Reviews. Drug Discovery·Konrad H BleicherAlexander I Alanine
Apr 21, 2004·Nature Biotechnology·Samu MelkkoDario Neri
Dec 2, 2006·The Journal of Organic Chemistry·Jonas W HøjfeldtKurt V Gothelf
Oct 9, 2007·Journal of the American Chemical Society·S Jarrett WrennPehr B Harbury
Jan 7, 2009·Journal of the American Chemical Society·Margit Haahr HansenNils Jakob Vest Hansen
Aug 4, 2009·Nature Chemical Biology·Matthew A ClarkBarry A Morgan
Feb 16, 2010·Nature Chemical Biology·Thomas Kodadek
Mar 30, 2010·Current Opinion in Chemical Biology·Matthew A Clark
Apr 16, 2010·Current Opinion in Chemical Biology·James E Biggs-HouckJared T Shaw
Aug 5, 2010·Journal of the American Chemical Society·Ralph E KleinerDavid R Liu
Dec 29, 2010·ACS Chemical Biology·Fabian BullerDario Neri
Jun 16, 2011·Chemical Society Reviews·Ralph E KleinerDavid R Liu
Feb 22, 2012·Nature Chemical Biology·George GeorghiouMarkus A Seeliger
May 1, 2012·Nature Reviews. Drug Discovery·Michael M Hann, György M Keserü
Oct 19, 2012·Organic & Biomolecular Chemistry·Claudia PercivalleSylvain Ladame
Feb 26, 2013·Prostaglandins & Other Lipid Mediators·Patricia L PodolinJames F Callahan
Mar 5, 2013·Drug Discovery Today·Albert C PanDavid E Shaw
Mar 5, 2013·Journal of Pharmaceutical Sciences·Rodrigo Alves MoreiraAntonio Alonso
Nov 1, 2009·Expert Opinion on Drug Discovery·Tara Renee Heitner, Nils Jakob Vest Hansen
Apr 11, 2013·Journal of Medicinal Chemistry·Jeremy S DischRobert B Perni
Jan 7, 2014·Nature Chemical Biology·Aidan G GilmartinRakesh Kumar
Mar 14, 2014·Nature Reviews. Cancer·Tracy L NeroMichael W Parker
Mar 29, 2014·Accounts of Chemical Research·Raphael M FranziniJörg Scheuermann
Apr 23, 2014·ACS Combinatorial Science·Todd M DoranThomas Kodadek
Aug 7, 2014·Chemical Communications : Chem Comm·Cheng CaoXiaoyu Li
Sep 23, 2014·Nature Chemistry·Derek B Lowe

❮ Previous
Next ❯

Citations

Sep 18, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Benjamin P Cossins, Alastair D G Lawson
Jan 29, 2016·ACS Chemical Biology·Hazem SalamonAndreas Brunschweiger
Nov 30, 2015·Current Opinion in Chemical Biology·Shelby K DoyleAngela N Koehler
Mar 18, 2016·Nature Protocols·Willy DecurtinsJörg Scheuermann
Feb 26, 2016·Journal of Medicinal Chemistry·Raphael M Franzini, Cassie Randolph
Dec 10, 2016·Nature Reviews. Drug Discovery·Robert A GoodnowAnthony D Keefe
Feb 16, 2017·ACS Combinatorial Science·Andrew B MacConnellBrian M Paegel
Jan 21, 2017·Chembiochem : a European Journal of Chemical Biology·Margherita Di PisaOliver Seitz
May 12, 2017·Current Opinion in Chemical Biology·Ruiwu LiuKit S Lam
May 10, 2017·Chemistry : a European Journal·Gunther ZimmermannDario Neri
Dec 25, 2016·Bioorganic & Medicinal Chemistry Letters·Bingbing ShiXiaoyu Li
Jun 13, 2018·Biological Chemistry·Verena KunigAndreas Brunschweiger
Apr 24, 2018·FEBS Letters·Nicholas FavalliDario Neri
Feb 19, 2016·Nature·Asher Mullard
Aug 21, 2019·Chemistry : a European Journal·Oleksandr O GrygorenkoDuncan B Judd
May 10, 2020·Nucleic Acids Research·Laurens LindenburgFlorian Hollfelder
May 20, 2020·Chemistry : a European Journal·Marianna RossettiAlessandro Porchetta
Dec 1, 2015·Chemical Science·Gang LiXiaoyu Li
Dec 5, 2020·Future Medicinal Chemistry·Daniel ConoleMichael J Waring
Feb 13, 2021·Journal of the American Chemical Society·Lars K PetersenNils J V Hansen
Apr 24, 2021·Chembiochem : a European Journal of Chemical Biology·Yiran Huang, Xiaoyu Li
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gita MatulevičiūtėAlgirdas Šačkus
May 11, 2020·Biochemical and Biophysical Research Communications·Gabriele BassiDario Neri
Mar 12, 2019·Journal of the American Chemical Society·Lik Hang YuenRaphael M Franzini
Aug 25, 2021·Accounts of Chemical Research·Yinan Song, Xiaoyu Li
Aug 24, 2021·ACS Pharmacology & Translational Science·Adrián Gironda-MartínezDario Neri
Nov 10, 2018·Journal of the American Chemical Society·Yu ZhouXiaoyu Li

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Current Opinion in Drug Discovery & Development
Richard S Pottorf, Mark R Player
Chembiochem : a European Journal of Chemical Biology
Jörg Scheuermann, Dario Neri
Current Opinion in Chemical Biology
Mahesh UttamchandaniYoung-Tae Chang
© 2022 Meta ULC. All rights reserved