Synthesis and bioassays of 3D sugar-based clusters for treating cancer

A key factor in metastasis (the migration of cancer cells to remote parts of the body) is an enzyme called heparanase. It releases chemicals from the extracellular matrix that encourage tumour growth. The primary tumour spreads to other tissues, becoming very difficult to treat. High levels of heparanase correlate with increased tumour size, enhanced metastasis and poor prognosis. These findings confirm heparanase as a highly druggable target for the cancer therapy. While standard anti-cancer drugs rapidly kill dividing cancer cells, they also affect normal cells, producing toxic side effects. New, more effective treatments are urgently needed. Because normal cells express very low levels of heparanase, negligible side effects are expected from blocking heparanase function.

The research will encompass two areas: first, chemical synthesis and modifications of bio-inspired heparanase inhibitors to improve protein binding while retaining systemic safety; second, labelling of inhibitors for visualisation in cell based assays and animal tissues.

This research project combines leading New Zealand and international expertise in medicinal chemistry and cancer biology. New compounds will be tested in a variety of in vitro and in vivo cancer models.

The successful candidate should have (or expect to have) an Honours Degree (or equivalent) in Organic chemistry, biochemistry or bioorganic chemistry.

This is a cross-disciplinary project involving elements of organic chemistry, carbohydrate chemistry and molecular biology. In this project, the Candidate will gain experience in chemical synthesis of dendrimers and carbohydrate molecules attached to fluorophores and tracers. The Candidate will learn characterization of 3D compounds by NMR and Mass Spectrometry analyses as well as cell-based assays techniques.