Protein chips, development

The development of protein chip assays to determine protein function using purified components is a rapidly advancing area. Automated systems for the assay of protein function on chips in parallel for thousands of proteins simultaneously will likely be available in the next few years. These miniaturized arrays will be useful for basic research as well as for diagnostics and drug development. For instance, the combination of protein chips with combinatorial chemistry will allow the simultaneous screening of vast collections of small molecules against vast collections of potential target proteins. 

Protein microchips have a significant impact on the development of safer drugs through the comprehensive profiling of drugs or lead compounds for effects. Zhu et al. [35] used a microarray of an entire eukaryotic proteome to screen different biochemical activities. First, protein chips can screen potential lead compounds at high throughput... 

Other early work includes that of Moody et al. (2001) who spotted anticytokine monoclonals onto the bottom of polystyrene microtiter plates (Max-isorp, Nalge Nunc) and measured cytokine levels in stimulated peripheral blood mononuclear cells. Finally, although not strictly a microarray, the microwell array system developed by Michael Snyder s group at Yale University to measure kinase activity is a simple and elegant approach (Zhu et al., 2000). The "protein chip" is comprised of microwells fabricated in a flexible elastomer of PDMS [poly(dimethylsiloxane)] substrate by a molding process. 

Protein Chips Proteins, too, can be immobilized on a solid surface and used to help define the presence or absence of other proteins in a sample. For example, researchers prepare an array of antibodies to particular proteins by immobilizing them as individual spots on a solid surface. A sample of proteins is added, and if the protein that binds any of the antibodies is present in the sample, it can be detected by a solid-state form of the ELISA assay (see Fig. 5-28). Many other types and applications of protein chips are being developed. 

Warren EN, Elms PJ, Parker CE, et al. Development of a protein chip a MS-based method for quantitation of protein expression and modification levels using an immunoaffmity approach. Anal. Chem. (2004) 76 4082-4092. 

Surface-enhanced laser/desorption ionization mass spectrometry Protein-Chip . See Tang, N., Tomatore, P, and Weinberger, S.R., Current developments in SELDI affinity technology. Mass Spectrom. Rev. 23a, 34-44,2004. 

Perhaps the area in proteomics that is generating most excitement at the moment is applications focusing on biomarker discovery. The development of protein chips, high-throughput mass spectrometry, and sensitive quantitation (ICAT, DICE, etc.) has provided a... 

Another method using protein "chips has also been developed (Haab et al., 2001 Zhao et al., 2001 Zhu et al., 2001). These chips contain ordered arrays of protein-binding molecules with the proteins then bound or enriched on a segment of the chip to be analyzed via various technologies. Antibodies recognizing specific protein sequences or modifications can be used, for example, to separate proteins with a specific activity from a complex mixture. A different version of a protein chip has been created by Zhu et al. (2001) and by Martzen et al. (1999). In these cases, the proteins are arrayed on the chip and the proteome can then be screened for interaction with particular substrates and ligands, and for certain classes of biochemical properties and activities. 

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