2009/12/08 by Brett Lomenick, Rui Hao, Nao Jonai +14 · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · Immunology and Microbiology · #RNA and protein synthesis mechanisms #Sirtuins and Resveratrol in Medicine #Toxin Mechanisms and Immunotoxins
paper · doi:10.1073/pnas.0910040106
openalex publication_date 2009/12/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.