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Quantitative chemical proteomics for identifying candidate drug targets
Yoshiya Oda1, Takashi Owa, Toshitaka Sato
1Laboratory of Seeds Finding Technology, Eisai Co., Ltd, Tokodai 5-1-3, Tsukuba, Ibaraki 300-2635, Japan. y-oda@hhc.eisai.co.jp
Analytical Chemistry
|May 2, 2003
Summary
This study introduces a systematic strategy for drug target identification using quantitative proteomics. The method identifies specific binding proteins for novel anticancer agents, advancing drug discovery.
Area of Science:
- Proteomics
- Drug Discovery
- Biochemistry
Background:
- Identifying specific drug target proteins is crucial for developing effective therapeutics.
- Existing methods for target identification can be limited in scope and sensitivity.
Purpose of the Study:
- To develop and validate a systematic, quantitative proteomics strategy for identifying drug target proteins.
- To demonstrate the application of this strategy in identifying the target of a novel anticancer agent.
Main Methods:
- Utilized differential affinity matrices for protein enrichment.
- Employed a cleavable isotope-coded affinity tag (ICAT) for protein labeling.
- Integrated liquid chromatography-mass spectrometry (LC-MS), transcription profiling, and surface plasmon resonance (SPR) for identification and validation.
Main Results:
- Successfully identified the primary binding protein for a novel class of anticancer agents (E7070).
- Demonstrated the capability of the method to quantify tagged peptides and select candidate proteins.
Conclusions:
- The developed strategy offers a novel quantitative proteomics approach for identifying specific binding proteins from complex mixtures.
- This method is broadly applicable to small molecules with unknown target proteins, facilitating drug discovery and development.