PDF icon Download PDF
Scheuermann, J.  et al.: 2024 Science of Synthesis, 2023/5: DNA-Encoded Libraries DOI: 10.1055/sos-SD-241-00252
DNA-Encoded Libraries

4.4 Selections of DNA-Encoded Libraries to Protein Targets within Living Cells

More Information

Book

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. S. ; 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;Chemical Reactions, Catalysis;Organometallic Chemistry;Laboratory Techniques, Stoichiometry

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

Also available at Science of Synthesis
 


B. Cai;   C. J. Krusemark 

Abstract

Zoom

Selections of DNA-encoded libraries (DELs) have been largely limited to biochemically pure proteins that are immobilized on solid supports. This excludes many targets that cannot be purified or reconstituted biochemically in a fully active form. This chapter describes a method for the selection of DEL ligands against proteins within live cells. The approach relies on appending a cyclic cell-penetrating peptide to the DNA construct to deliver DELs across the cell membrane into the cytoplasm of live cells. Once inside the cell, affinity crosslinking is used to covalently trap protein–ligand interactions. The DEL ligands are isolated by subsequent purification of the target protein. This approach has demonstrated potential in selecting focused libraries against cytosolic targets that are challenging to express and purify.

Key words

DNA-encoded libraries - crosslinking - cyclic cell-penetrating peptides - drug discovery - selections
 
  • 17 Ma H, Murray JB, Luo H, Cheng X, Chen Q, Song C, Duan C, Tan P, Zhang L, Liu J, Morgan BA, Li J, Wan J, Baker LM, Finnie W, Guetzoyan L, Harris R, Hendrickson N, Matassova N, Simmonite H, Smith J, Hubbard RE, Liu G. RSC Med. Chem. 2022; 13: 1341
    CrossrefPubMedSearch in Google Scholar