Identification of Direct Protein Targets of Small Molecules

被引：237

作者：

Lomenick, Brett ^{[1
]}

Olsen, Richard W. ^{[1
]}

Huang, Jing ^{[1
]}

机构：

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

来源：

ACS CHEMICAL BIOLOGY | 2011年 / 6卷 / 01期

基金：

美国国家卫生研究院;

关键词：

2D-PAGE; Affinity chromatography; Degradomics; Drug affinity responsive target stability (DARTS); MudPIT; SILAC; Target identification; CYTOSOLIC BINDING-PROTEIN; HUMAN GROWTH-HORMONE; NATURAL-PRODUCTS; FKBP12-RAPAMYCIN COMPLEX; IMMUNOSUPPRESSANT FK506; LIQUID-CHROMATOGRAPHY; COLCHICINE-BINDING; MAMMALIAN PROTEIN; CHEMICAL GENETICS; HYDROGEN-EXCHANGE;

D O I：

10.1021/cb100294v

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Small-molecule target identification is a vital and daunting task for the chemical biology community as well as for researchers interested in applying the power of chemical genetics to impact biology and medicine. To overcome this "target ID" bottleneck, new technologies are being developed that analyze protein drug interactions, such as drug affinity responsive target stability (DARTS), which alms to discover the direct binding targets (and off targets) of small molecules on a proteome scale without requiring chemical modification of the compound. Here, we review the DARTS method, discuss why it works, and provide new perspectives for future development in this area.

引用

页码：34 / 46

页数：13

共 127 条

[1] Methods for the proteomic identification of protease substrates [J].

Agard, Nicholas J. ;

Wells, James A. .

CURRENT OPINION IN CHEMICAL BIOLOGY, 2009, 13 (5-6) :503-509

[2] Chemical genetics screen for enhancers of rapamycin identifies a specific inhibitor of an SCF family E3 ubiquitin ligase [J].

Aghajan, Mariam ;

Jonai, Nao ;

Flick, Karin ;

Fu, Fei ;

Luo, Manlin ;

Cai, Xiaolu ;

Ouni, Ikram ;

Pierce, Nathan ;

Tang, Xiaobo ;

Lomenick, Brett ;

Damoiseaux, Robert ;

Hao, Rui ;

del Moral, Pierre M. ;

Verma, Rati ;

Li, Ying ;

Li, Cheng ;

Houk, Kendall N. ;

Jung, Michael E. ;

Zheng, Ning ;

Huang, Lan ;

Deshaies, Raymond J. ;

Kaiser, Peter ;

Huang, Jing .

NATURE BIOTECHNOLOGY, 2010, 28 (07) :738-U1750

[3] MASS-SPECTROMETRIC CHARACTERIZATION OF A PROTEIN LIGAND INTERACTION [J].

ANDEREGG, RJ ;

WAGNER, DS .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (04) :1374-1377

[4]

ARSENIS C, 1964, J BIOL CHEM, V239, P3093

[5] A label-free quantification method by MS/MS TIC compared to SILAC and spectral counting in a proteomics screen [J].

Asara, John M. ;

Christofk, Heather R. ;

Freimark, Lisa M. ;

Cantley, Lewis C. .

PROTEOMICS, 2008, 8 (05) :994-999

[6] Curcumin Disrupts the Mammalian Target of Rapamycin-Raptor Complex [J].

Beevers, Christopher S. ;

Chen, Long ;

Liu, Lei ;

Luo, Yan ;

Webster, Nicholas J. G. ;

Huang, Shile .

CANCER RESEARCH, 2009, 69 (03) :1000-1008

[7] 2 DISTINCT SIGNAL TRANSMISSION PATHWAYS IN LYMPHOCYTES-T ARE INHIBITED BY COMPLEXES FORMED BETWEEN AN IMMUNOPHILIN AND EITHER FK506 OR RAPAMYCIN [J].

BIERER, BE ;

MATTILA, PS ;

STANDAERT, RF ;

HERZENBERG, LA ;

BURAKOFF, SJ ;

CRABTREE, G ;

SCHREIBER, SL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (23) :9231-9235

[8] Unnatural ligands for engineered proteins: New tools for chemical genetics [J].

Bishop, A ;

Buzko, O ;

Heyeck-Dumas, S ;

Jung, I ;

Kraybill, B ;

Liu, Y ;

Shah, K ;

Ulrich, S ;

Witucki, L ;

Yang, F ;

Zhang, C ;

Shokat, KM .

ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE, 2000, 29 :577-606

[9] Natural Products and Their Biological Targets: Proteomic and Metabolomic Labeling Strategies [J].

Boettcher, Thomas ;

Pitscheider, Maximilian ;

Sieber, Stephan A. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2010, 49 (15) :2680-2698

[10] Selective targeting of lysosomal cysteine proteases with radiolabeled electrophilic substrate analogs [J].

Bogyo, M ;

Verhelst, S ;

Bellingard-Dubouchaud, V ;

Toba, S ;

Greenbaum, D .

CHEMISTRY & BIOLOGY, 2000, 7 (01) :27-38

← 1 2 3 4 5 6 7 8 9 10 →