Phosphorylation of proteins and metabolites is an essential mechanism for signal transduction and propagation in the cell and thus of utmost importance for cellular function. In spite of this, there is a lack of synthetic chemical receptors for the detection and separation of phosphoesters that combine selectivity and sensitivity. In this project we aim to develop novel chemical receptors for the efficient recognition of phosphorylated molecules of biological interest. The design of such receptors will be based on metallo-receptors that combine strong binding (through metal-phosphate interactions) with high selectivity (provided by hydrogen-bonding groups and other reversible interactions). In order to assemble the different components of the receptors, we propose to use dynamic combinatorial chemistry (DCC) using the phosphorylated species of interest as templates to “amplify” the best receptors from the virtual dynamic combinatorial library. Once the best receptors are identified using the above methodology and their selectivity and sensitivity are optimised, they will be used for the development of chemical sensors to detect specific phosphorylated species. This will be carried out by incorporating optical labels that change their properties upon binding between receptor and phosphorylated guest. Particular emphasis will be given to the detection of phosphorylated phosphoinositides since they play important roles in cell signalling and regulation and their levels can be correlated to the molecular basis of certain diseases.
Field of science
- /natural sciences/biological sciences/cell biology/cell signaling
Call for proposal
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