Phosphorylated inositols and phosphatidylinositol phosphates are two important classes of intracellular second messengers. myo-Inositol 1,4,5-trisphosphate (InsP3) is generated in response to activation of G-protein coupled receptors and releases calcium from intracellular stores. This calcium release leads to a plethora of important cellular events, including gene transcription, muscle contraction and cell proliferation. We are engaged in the synthesis of novel InsP3 derivatives that will allow us to further probes the intracellular function of InsP3 receptors (InsP3Rs). In particular, we have been synthesising InsP3 derivatives that are modified at the 4-position and investigating their activity as InsP3R antagonists. (see Bello et al., J. Org. Chem. 2007).

Phosphatidylinositol polyphosphate exert their biological action through interaction with specific binding domains of certain protein targets. Once such domain is the pleckstrin homology (PH) domain. We are developing novel compounds that will prevent binding of phosphatidylinositols to PH domains and hence prevent their cellular action.