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  • Title: Microarray-based enzyme profiling: Recent advances and applications (Review).
    Author: Uttamchandani M, Moochhala S.
    Journal: Biointerphases; 2010 Sep; 5(3):FA24-31. PubMed ID: 21171709.
    Abstract:
    Enzymes are an integral part of biological systems. They constitute a significant majority of all proteins expressed (an estimated 18%-29%) within eukaryotic genomes. It thus comes as no major surprise that enzymes have been implicated in many diseases and form the second largest group of drug targets, after receptors. Despite their involvement in a multitude of physiological processes, only a limited number of enzymes have thus far been well-characterized. Consequently, little is understood about the physiological roles, substrate specificity, and downstream targets of the vast majority of these important proteins. In order to facilitate the biological characterization of enzymes, as well as their adoption as drug targets, there is a need for global "-omics" solutions that bridge the gap in understanding these proteins and their interactions. Herein the authors showcase how microarray methods can be adopted to facilitate investigations into enzymes and their properties, in a high-throughput manner. They will focus on several major classes of enzymes, including kinases, phosphatases, and proteases. As a result of research efforts over the last decade, these groups of enzymes have become readily amenable to microarray-based profiling methods. The authors will also describe the specific design considerations that are required to develop the appropriate chemical tools and libraries to characterize each enzyme class. These include peptide substrates, activity-based probes, and chemical compound libraries, which may be rapidly assembled using efficient combinatorial synthesis or "click chemistry" strategies. Taken together, microarrays offer a powerful means to study, profile, and also discover potent small molecules with which to modulate enzyme activity.
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