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Selection of DNA-Encoded Libraries to Protein Targets within and on Living Cells
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Date
2019-10-01
Author
Cai, Bo
Kim, Dongwook
Akhand, Saeed
Sun, Yixing
Cassell, Robert J.
Alpsoy, Aktan
Dykhuizen, Emily C.
Van Rijn, Richard M.
Wendt, Michael K.
Krusemark, Casey J.
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Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
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We report the selection of DNA-encoded small molecule libraries against protein targets within the cytosol and on the surface of live cells. The approach relies on generation of a covalent linkage of the DNA to protein targets by affinity labeling. This cross-linking event enables subsequent copurification by a tag on the recombinant protein. To access targets within cells, a cyclic cell-penetrating peptide is appended to DNA-encoded libraries for delivery across the cell membrane. As this approach assesses binding of DELs to targets in live cells, it provides a strategy for selection of DELs against challenging targets that cannot be expressed and purified as active.
URI
https://hdl.handle.net/11511/117326
Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
DOI
https://doi.org/10.1021/jacs.9b08085
Collections
Department of Biology, Article
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B. Cai et al., “Selection of DNA-Encoded Libraries to Protein Targets within and on Living Cells,”
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
, vol. 141, no. 43, pp. 17057–17061, 2019, Accessed: 00, 2025. [Online]. Available: https://hdl.handle.net/11511/117326.