Open AccessSelection of DNA-Encoded Libraries to Protein Targets within and on Living Cells
Author(s) -
Bo Cai,
Dong-Wook Kim,
Saeed Salehin Akhand,
Yubo Sun,
Robert J. Cassell,
Aktan Alpsoy,
Emily C. Dykhuizen,
Richard M. van Rijn,
Michael K. Wendt,
Casey J. Krusemark
Publication year - 2019
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.9b08085
Subject(s) - chemistry , dna , recombinant dna , selection (genetic algorithm) , cytosol , cell , genomic library , computational biology , gene , microbiology and biotechnology , biochemistry , enzyme , biology , base sequence , artificial intelligence , computer science
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.