Journal article
Selection of DNA-Encoded Libraries to Protein Targets within and on Living Cells
Journal of the American Chemical Society, Vol.141(43), pp.17057-17061
10/30/2019
DOI: 10.1021/jacs.9b08085
PMCID: PMC7057806
PMID: 31613623
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.
Details
- Title: Subtitle
- Selection of DNA-Encoded Libraries to Protein Targets within and on Living Cells
- Creators
- Bo Cai - Purdue University West LafayetteDongwook Kim - Purdue University West LafayetteSaeed Akhand - Purdue University West LafayetteYixing Sun - Purdue University West LafayetteRobert J. Cassell - Purdue University West LafayetteAktan Alpsoy - Purdue University West LafayetteEmily C. Dykhuizen - Purdue University West LafayetteRichard M. Van Rijn - Purdue University West LafayetteMichael K. Wendt - Purdue University West LafayetteCasey J. Krusemark - Purdue University West Lafayette
- Resource Type
- Journal article
- Publication Details
- Journal of the American Chemical Society, Vol.141(43), pp.17057-17061
- DOI
- 10.1021/jacs.9b08085
- PMID
- 31613623
- PMCID
- PMC7057806
- NLM abbreviation
- J Am Chem Soc
- ISSN
- 0002-7863
- eISSN
- 1520-5126
- Publisher
- Amer Chemical Soc
- Number of pages
- 5
- Grant note
- R03DA045897 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission Lilly Endowment R21AA026949 / NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) 1R35GM128894-01; CA207532; AA025368; AA026949; AA026675; DA045897 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R35GM128894 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) P30 CA023168 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA RSG-16-172-01 / American Cancer Society U01CA207532 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 10/30/2019
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984460332202771
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