期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 141, 期 43, 页码 17057-17061出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.9b08085
关键词
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资金
- NIH [1R35GM128894-01, CA207532, AA025368, AA026949, AA026675, DA045897]
- American Cancer Society [RSG-16-172-01]
- Lilly Endowment
- National Institutes of Health [P30 CA023168]
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.
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