Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 51, Pages 21984-21989Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0910040106
Keywords
aging; label-free; proteomics; small molecules
Categories
Funding
- National Institutes of Health National Cancer Institute [R01 CA124974]
- American Cancer Society [RSG-07-035-01-CCG]
- National Institutes of Health UCLA Chemistry-Biology Interface Predoctoral Training [T32 GM008496]
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Identifying the molecular targets for the beneficial or detrimental effects of small-molecule drugs is an important and currently unmet challenge. We have developed a method, drug affinity responsive target stability (DARTS), which takes advantage of a reduction in the protease susceptibility of the target protein upon drug binding. DARTS is universally applicable because it requires no modification of the drug and is independent of the mechanism of drug action. We demonstrate use of DARTS to identify known small-molecule-protein interactions and to reveal the eukaryotic translation initiation machinery as a molecular target for the longevity-enhancing plant natural product resveratrol. We envisage that DARTS will also be useful in global mapping of protein-metabolite interaction networks and in label-free screening of unlimited varieties of compounds for development as molecular imaging agents.
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