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Scheuermann, J.  et al.: 2024 Science of Synthesis, 2023/5: DNA-Encoded Libraries DOI: 10.1055/sos-SD-241-00296
DNA-Encoded Libraries

5.2 On-DNA Resynthesis and Affinity Selection Mass Spectrometry (ASMS)

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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. 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

A limitation of the split-and-pool approach in creating DNA-encoded libraries (DELs) is that DNA-conjugated side products and starting materials generally cannot be removed during DEL production. Consequently, the same DNA barcode encodes all the products generated during library synthesis (including byproducts) rather than just a single product. In the use of off-DNA resynthesis to confirm hits after affinity selection, a “one-to-one” relationship between the DNA tag and the structure of the attached molecule it encodes is often assumed. However, because library synthesis often yields a mixture, this approximation increases the risk of overlooking positive discoveries and valuable information. On-DNA resynthesis, using the same building blocks and chemical reactions as in DEL production, can be employed to obtain a product mixture similar to that observed during the original library production. This mixture of on-DNA compounds can then be directly tested using affinity selection mass spectrometry (ASMS). This chapter outlines ASMS as a technique to assay low-complexity mixtures of molecules for target-protein binding, including discussion of the two primary types of ASMS: on-DNA and cleaved.

Key words

DNA-encoded libraries - affinity selection mass spectrometry (ASMS) - on-DNA ASMS - cleaved ASMS - on-DNA resynthesis - drug discovery - photocleavable linkers
 
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