Sulforaphane and alliin are known to be the cardioprotective “ingredients” in broccoli and onion diets. They have been shown to promote cardiomyocyte survival against ischaemic injury and exhibit potent anticancer activity by potentiating apoptosis. However, the protein target spectra of these small molecules in cells remain unclear. There is no unified model to explain the cell-type-dependent phenotypes observed in the treatment. Therefore, the specific aims of the first arm of this project are to: (i) profile the cell-type-specific target spectra of sulforaphane and alliin and forge a molecular link between protein target engagement and phenotypic outcome; and (ii) engineer small-molecule transport proteins targeting specific organelles to enable protein target profiling of sulforaphane and alliin in a spatiotemporally controlled manner.
In collaboration with the Payne research group (School of Chemistry, USYD), the specific aims of the second arm of this project are to: (i) optimise the efficacy and mitigate the cardiotoxicity of current chemotherapy through conjugation with cardiovascular-protective natural products; and (ii) apply “click-and-release” chemistry to develop antibody-small-molecule conjugates enabling organ- and tissue-specific release of sulforaphane and alliin.