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 anti-cancer 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, The University of Sydney), 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.