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Selection of DNA-Encoded Libraries to Protein Targets within and on Living Cells
Journal article   Open access   Peer reviewed

Selection of DNA-Encoded Libraries to Protein Targets within and on Living Cells

Bo Cai, Dongwook Kim, Saeed Akhand, Yixing Sun, Robert J. Cassell, Aktan Alpsoy, Emily C. Dykhuizen, Richard M. Van Rijn, Michael K. Wendt and Casey J. Krusemark
Journal of the American Chemical Society, Vol.141(43), pp.17057-17061
10/30/2019
DOI: 10.1021/jacs.9b08085
PMCID: PMC7057806
PMID: 31613623
url
https://www.ncbi.nlm.nih.gov/pmc/articles/7057806View
Open Access

Abstract

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.
Physical Sciences Chemistry Chemistry, Multidisciplinary Science & Technology

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