Target identification using drug affinity responsive target stability (DARTS)

被引：903

作者：

Lomenick, Brett ^{[1
,2
]}

Hao, Rui ^{[1
,2
]}

Jonai, Nao ^{[1
,2
]}

Chin, Randall M. ^{[1
,2
]}

Aghajan, Mariam ^{[1
,2
]}

Warburton, Sarah ^{[3
]}

Wang, Jianing ^{[4
]}

Wu, Raymond P. ^{[1
,2
]}

Gomez, Fernando ^{[5
]}

Loo, Joseph A. ^{[4
,5
]}

Wohlschlegel, James A. ^{[4
]}

Vondriska, Thomas M. ^{[3
]}

Pelletier, Jerry ^{[6
]}

Herschman, Harvey R. ^{[1
,2
,4
]}

Clardy, Jon ^{[7
]}

Clarke, Catherine F. ^{[5
]}

Huang, Jing ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Biol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol Med Cardiol & Physiol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA

[6] McGill Univ, Dept Biochem, Montreal, PQ, Canada

[7] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 51期

基金：

美国国家卫生研究院;

关键词：

aging; label-free; proteomics; small molecules; PROTEIN EXPRESSION; CHEMICAL GENETICS; MASS-SPECTROMETRY; GLOBAL ANALYSIS; SMALL MOLECULES; LIGAND-BINDING; TOR PATHWAY; LIFE-SPAN; YEAST; GENOME;

D O I：

10.1073/pnas.0910040106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：21984 / 21989

页数：6

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