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Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21984-9. doi: 10.1073/pnas.0910040106. Epub 2009 Dec 7.

Target identification using drug affinity responsive target stability (DARTS).

Author information

1
Department of Molecular and Medical Pharmacology and the Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

Abstract

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.

PMID:
19995983
PMCID:
PMC2789755
DOI:
10.1073/pnas.0910040106
[Indexed for MEDLINE]
Free PMC Article

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