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

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.

SUBMITTER: Cai B

PROVIDER: S-EPMC7057806 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Cai Bo B Kim Dongwook D Akhand Saeed S Sun Yixing Y Cassell Robert J RJ Alpsoy Aktan A Dykhuizen Emily C EC Van Rijn Richard M RM Wendt Michael K MK Krusemark Casey J CJ

Journal of the American Chemical Society 20191022 43

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 appro ...[more]

PMID: 31613623

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