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Development of Novel Enzyme Inhibitors for Anticancer Applications

This talk will cover two of our research areas aimed at developing improved cancer treatments through computational drug design and synthetic chemistry. The first project describes our approach to modulate cell surface sialylation. Sialic acid is found at the terminus of most cell-surface glycoconjugates where it mediates cell recognition, migration, receptor binding and immune responses. Sialyltransferase (ST) enzymes catalyse sialylation and are upregulated in many advanced cancers correlating with poor patient outcomes. As a result, inhibiting STs is being pursued as a new anti-cancer strategy. However, for clinical applications ST selectivity and cell permeability remain a challenge. Guided by in silico modelling, we have developed a leading series of selective ST inhibitors, replacing the charged phosphodiester linker with a neutral bioisostere to enhance drug-like properties and improve synthetic accessibility. In the second part, I will present our collaboration with ANSTO developing radiosensitisers and a range of boron-containing compounds for Neutron Capture Enhanced Particle Therapy (NCEPT), an innovative radiotherapy technique pioneered by ANSTO/UOW to treat aggressive cancers including brain tumours, pancreatic cancer and melanoma.

Biography

Danielle Skropeta is a Professor of Medicinal Chemistry and Associate Dean of Higher Degree Research at the University of Wollongong (UOW). Danielle completed her PhD at ANU under the supervision of Prof Rod Rickards, followed by postdoctoral positions in Germany (with Prof Richard R Schmidt), Italy (with Prof Francesco Pietro) and Australia (with Prof Kate Jolliffe). She was a Senior Fellow at the Heart Research Institute before commencing her independent academic career at UOW in 2006. Danielle is currently a Fellow and Board Member of the Royal Australian Chemical Institute (RACI), Senior Fellow of the Higher Education Academy UK and former National STEM Ambassador for Science and Technology Australia. Danielle leads an interdisciplinary research group developing new anti-cancer agents & bioinspired solutions for bacterial infection & wound healing performed in collaboration with long-term industry and community partners. In 2020, she received the RACI Margaret Sheil National Leadership award for her advocacy of gender equity in the chemical sciences.