Pharmacoproteomic Approaches

General consensus has sub-divided proteomics into three main areas, Expression Proteomics, Functional Proteomics, and Structural Proteomics. Expression Proteomics (sometimes called differential-expression proteomics) involves the analysis of differential protein expression by protein 

In contrast, Functional Proteomics concerns the manner in which proteins interact and, in turn, how these interactions determine function, both normal and abnormal. This approach is less reductionist than Expression Proteomics as proteins are studied in the context of their complex cellular interactions. Finally, Structural Proteomics is concerned with the primary through tertiary structure of proteins, and modifications therein, largely determined by x-ray and NMR analysis of protein crystals (20). In this chapter we will concern ourselves only with Expression and Functional Proteomics. 

The classical combination of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) (Fig. 1) remains the most widely used approach in proteomic analysis. This figure also illustrates the additional use of tandem 

either after electrophoretic separation and proteolysis or independently of 2DE [e.g., as in Multidimensional Protein Identification Technology (MudPIT), Ref. 21, also see Sec. 3.1.3), as a stand-alone system for protein identification. 

Nuclei/Plasma Membrane Mitochondria Microsomes Cytosdl Protein Assay 

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Since disease processes lead to protein changes, it is of paramount importance to consider the relationship between disease and therapy at the protein level (Anderson and Anderson 1998). The objective of modern pharmacoproteomics is the identification of phenotypic differences in drug metabohsm or response and the subsequent examination of candidate proteins for variations that underUe the observed phenotypes. Instead of focusing on a few protein targets, pharmacoproteomics takes a more global approach in order to capture complicated patterns of protein expression (Anderson and Anderson 1998 Petricoin III et al. 2002). 

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