Synthesis and Functions of Inositol Phosphates

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My research program aims at developing chemical biology tools to study inositol phosphates, an important family of endogenous molecules. Inositol phosphates play numerous crucial roles in the cell, ranging from cellular signalling and calcium mobilization to transcription regulation. Furthermore, some inositol phosphates are also anchored in the lipid bilayer where they recruit a multitude of proteins with important biological consequences. Despite the crucial functions of inositol phosphates in cell, a comprehensive picture is still lacking. This is due in part to the fact that there are over 60 possible inositol phosphate variations depending on the degree and position of phosphorylation. In addition, inositol phosphates interact with a daunting number of proteins. Access to well defined inositol phosphate molecules and their analogues is of key importance to decipher their precise role and mechanism at a molecular level. Moreover, the strong binding of inositol phosphates to calcium and other physiological cations has a dramatic impact on their functions. The ability to modulate the ion binding properties of inositol phosphates will provide important chemical tools. In addition, the chelating properties of inositol phosphates can be exploited to afford new biocompatible coating agents for inorganic surfaces, with potential applications in functional materials. In this research program I aim to develop novel synthetic methods to prepare natural inositol phosphates and their unnatural analogues. These methods will be used to prepare innovative chemical tools to understand the interactions of inositol phosphates with proteins and their function in cells. To that effect, the development of a delivery system for inositol phosphates will be necessary in order to bring the inositol phosphates to the cell cytosol. A second general aim will be to harness the cation binding properties of inositol phosphates to develop better coating agents for inorganic material such as calcium phosphate used in biomedical applications. In addition, various anti-fouling and anti-bacterial coating for functional materials will be prepared. Furthermore, the binding of inositol phosphates to the bone mineral hydroxyapatite will be exploited to design a better bone-binding agent. Based on this, next-generation imaging agents capable of detecting specific enzymatic activity in bone tissues will be developed to study important bone processes such as bone formation and dissolution in vivo. The importance of inositol phosphates in biology warrants the development of the chemical tools proposed here. The molecules will provide essential fundamental knowledge, but also new functional materials and imaging probes for bone tissues, with implications in novel diagnosis modalities for bone disorders.