Differential sensing of kinases.
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During the last decade, organic and supramolecular chemistry in combination with analytical and fluorescent-based sensing methods have led to the development of chemical biology tools to study protein phosphorylation in vitro. However, further challenges remain present to develop better chemical approaches that can allow us to understand the activation/inhibition of specific kinase pathways. To avoid the tedious process of developing individual highly selective receptors, the use of differential sensing techniques has been growing in the supramolecular chemistry field. This sensing protocol exploits the interactions between target analytes and a library of cross-reactive receptors to create a response pattern that is unique for individual analytes or different mixtures thereof. Using this approach, one obtains a distinct fingerprint of composite signals produced by the sensor elements allowing for discrimination of different kinases in vitro and in complex mixtures such as cell lysates. The main emphasis of this work sought to expand the current optical-based detection systems of phosphorylated proteins to include a new pattern-based recognition method for a new class of protein kinases. To this end, the synthesis of chemosensors and peptide-based biosensors was pursued to detect and differentiate relevant mitogen-activated protein (MAP) kinases which represent targets of pharmaceutical interest. Further, this research included the quantitative detection of MAP kinases and corresponding inhibitors using a combination of pattern recognition approaches with new chemometric tools.