Medicinal Chemistry Reviews

Volume 52, Chapter 20

SILAC Proteomics in Drug Discovery

Thomas M. Graczyk, James P. Finn, and Ravi R. Iyer

1.          Introduction                                                                                                               383

            1.1        Overview                                                                                                        383

            1.2        Proteomics Approaches to Understanding Biological Function              385

                        1.2.1     SILAC                                                                                      385

                        1.2.2     Isobaric Tagging-Coupled Mass Spectrometry                               385

2.         SILAC Analysis Strategies                                                                              386

            2.1        SILAC Labeling and Global Proteome Analysis in Cultured Cells             386

            2.2       Application of SILAC to Analysis of Post-Translational Modifications 

                        and Protein Interaction Networks                                                               387

            2.3       SILAC Strategies for Whole Animal and Human Studies               392

3.         SILAC Proteomics in Drug Discovery                                                                       393

            3.1        Target Discovery and Pathway Biology                                                      393

            3.2       Compound Mechanism of Action                                                               395

            3.3       Biomarker Discovery                                                                         398

4.         Limitations of SILAC                                                                                                 398

5.         Conclusions                                                                                                               398

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