Identification of drug targets in vitro and in living cells by soluble-nanopolymer-based proteomics.
Identification of drug targets in vitro and in living cells by soluble-nanopolymer-based proteomics.
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DOI：
10.1002/anie.201006459
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发表时间：
2011-04-26
影响因子：
16.6
通讯作者：
Tao, W. Andy
中科院分区：
文献类型：
--
作者：
Hu, Lianghai;Iliuk, Anton;Galan, Jacob;Hans, Michael;Tao, W. Andy
High throughput drug discovery methods typically focus on protein targets which are screened in vitro against existing compounds for high specificity and affinity. This strategy, however, could result in unexpected or undetected off-targets effects, leading to high abrasion rates in the later stages of drug development. Ideally, unbiased identification of proteins and associated complexes that bind to a drug or drug candidate would provide direct evaluation and therefore would be more appealing, allowing for valuable insight into target cellular functions.[1] One of the most widely applied approaches to characterize proteins that bind specifically to candidate compounds is based on affinity chromatography combined with mass spectrometric identification.[2] However, the strategy is typically based on a solid support that can only capture potential protein targets in vitro but not in living systems. To address this, activity-based protein profiling (ABPP) strategy has been successfully introduced to study enzyme families both in vitro and in vivo.[3] The ABPP probes are based on either covalent reaction with the target proteins or photoaffinity labeling by incorporation of photoreactive groups. One important issue to consider is that a lot of important ligands are either hydrophobic or negatively charged, making direct delivery into living cells extremely challenging. Therefore, it is highly desirable to establish a general in situ approach to probe intracellular protein targets.Here we introduce a proteomic strategy based on soluble nanopolymers in an attempt to identify drug targets in vitro and from cells in culture. Soluble nanopolymers such as dendrimers are highly branched nanomolecules with attractive properties as drug delivery vehicles and as imaging contrast agents. Dendrimers have excellent solubility, high structural homogeneity, controlled surface functionalities, cells permeation ability and low cytotoxicity.[4, 5] We have previously used dendrimers as tools for isotope labeling-based quantitative proteomic and phosphoproteomic studies by chemically modifying them with
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影响因子：
7.3
作者：
Majoros, IJ;Thomas, TP;Baker, JR
通讯作者：
Baker, JR
影响因子：
7
作者：
Ong, SE;Blagoev, B;Mann, M
通讯作者：
Mann, M
使用定量质谱和珠蛋白质组识别特定的蛋白质相互作用伙伴。
影响因子：
7.8
作者：
Trinkle-Mulcahy, Laura;Boulon, Severine;Lam, Yun Wah;Urcia, Roby;Boisvert, Francois-Michel;Vandermoere, Franck;Morrice, Nick A.;Swift, Sam;Rothbauer, Ulrich;Leonhardt, Heinrich;Lamond, Angus
通讯作者：
Lamond, Angus
影响因子：
7
作者：
Iliuk, Anton B.;Martin, Victoria A.;Tao, W. Andy
通讯作者：
Tao, W. Andy
DOI：
10.1016/j.jchromb.2006.12.047
发表时间：
2007-08-01
影响因子：
3
作者：
Katayama, Hiroyuki;Oda, Yoshiya
通讯作者：
Oda, Yoshiya