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Scheuermann, J.  et al.: 2024 Science of Synthesis, 2023/5: DNA-Encoded Libraries DOI: 10.1055/sos-SD-241-00259
DNA-Encoded Libraries

3.2.1.1 Encoding Using Double-Stranded DNA: A Headpiece-Based DNA Ligation Strategy

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Editors: Scheuermann, J. ; Li, Y. 

Authors: Barluenga, S. ; Bassi, G. ; Brunschweiger, A. ; Cai, B. ; Cazzamalli, S. ; Chheda, P. ; Cui, M. ; Cui, W. ; Fang, X. ; Farrera-Soler, L. ; Favalli, N. ; Feng, J.; Foley, T. L. ; Franzini, R. M. ; Georgiev, T. ; Gillingham, D. ; Gloger, A. ; Graham, J. D. ; Granados, A. ; Heiden, S.; Hou, W. ; Huang, Y. ; Keefe, A. D. ; Krusemark, C. J. ; Li, X. ; Li, Y. ; Lin, W. ; Litovchick, A.; Liu, G. ; Lu, X. ; Lucaroni, L. ; Ma, P. ; Migliorini, F. ; Molander, G. A. ; Neri, D. ; Nie, Q. ; Oehler, S. ; Prati, L. ; Puglioli, S. ; Reddavide, F. V. ; Satz, A. L. ; Sauter, B. ; Scheuermann, J. ; Schuman, D.; Simmons, N. ; Stanway-Gordon, H. A. ; Su, W. ; Sun, J. ; Thompson, M.; Vummidi, B. R.; Wang, X. ; Wang, Y. ; Wang, Z. ; Waring, M. J. ; Willems, S.; Winssinger, N. ; Xia, B. ; Xiong, F. ; Xu, H. ; Xu, L. ; Yang, G. ; Zhang, G. ; Zhang, Y. ; Zhou, Y. 

Title: DNA-Encoded Libraries

Print ISBN: 9783132455221; Online ISBN: 9783132437357; Book DOI: 10.1055/b000000342

1st edition © 2024. Thieme. All rights reserved.
Georg Thieme Verlag KG, Stuttgart

Subjects: Organic Chemistry

Science of Synthesis Reference Libraries



Parent publication

Title: Science of Synthesis

DOI: 10.1055/b-00000101

Series Editors: Fürstner, A. (Editor-in-Chief); Carreira, E. M.; Faul, M.; Kobayashi, S.; Koch, G.; Molander, G. A.; Nevado, C.; Trost, B. M.; You, S.-L.

Type: Multivolume Edition

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Abstract

DNA-encoded chemical libraries (DELs) provide a powerful high-throughput screening platform that is used in both academia and industry. High-quality DELs lay the foundation for reliable DEL selection outcomes, and most pharmaceutical companies would prefer double-stranded DELs (dsDELs) because of their superior stability. Here, we summarize the experimental details for encoding a dsDEL, including the overall encoding strategy, synthetic chemistry of building-block addition, ligation strategies of code elongation, and quality control of the resulting libraries, exemplified with a 320-million-membered benzimidazole dsDEL from GlaxoSmithKline (GSK). We also briefly review the successful selection cases involving the presented libraries to highlight the great potential of dsDELs in drug discovery.

Key words

DNA-encoded libraries - double-stranded DNA-encoded libraries - DNA-encoded benzimidazole libraries - DNA-compatible chemistry - benzimidazoles - headpiece DNA - DNA-recorded libraries - split-and-pool - chemical ligation - enzymatic ligation - building blocks - high-throughput screening - drug discovery
 
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