title: Target identification using drug affinity responsive target stability (DARTS).
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.
authors.affiliation: Department of Molecular and Medical Pharmacology and the Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Lomenick
authors.forename: Rui
authors.initials: R
authors.lastname: Hao
authors.forename: Nao
authors.initials: N
authors.lastname: Jonai
authors.forename: Randall M
authors.initials: RM
authors.lastname: Chin
authors.forename: Mariam
authors.initials: M
authors.lastname: Aghajan
authors.forename: Sarah
authors.initials: S
authors.lastname: Warburton
authors.forename: Jianing
authors.initials: J
authors.lastname: Wang
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Wu
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomez
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Loo
authors.forename: James A
authors.initials: JA
authors.lastname: Wohlschlegel
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Vondriska
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
authors.forename: Harvey R
authors.initials: HR
authors.lastname: Herschman
authors.forename: Jon
authors.initials: J
authors.lastname: Clardy
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Clarke
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
mesh_terms: D001665:Binding Sites; D018076:DNA, Complementary; D016503:Drug Delivery Systems; D040901:Proteomics; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D013267:Stilbenes; D000077185:Resveratrol