Houston Group

Supervisors: Assoc Prof Todd A Houston, Assoc Prof Milton J Kiefel

Medicinal Chemistry

Boronic acids form covalent, but reversible, interactions with polyols such as sugars in aqueous solution. We have developed boronate receptors selective for cell-surface carbohydrates from both mammalian and bacterial cells (specifically sialic acid and KDO). Our receptors display a unique and divergent fluorescent response that can be exploited for selective detection in biological media. Ultimately, these receptors will be developed into boronolectins that target specific cell types and may be used in drug targeting.  These synthetic receptors can identify targets complementary to those of nature’s antibodies and lectins that normally survey cell surfaces.  In addition, we have identified anti-bacterial activity in some of these compounds implying there is potential to develop these into medicinal agents.

Techniques: Synthetic chemistry; fluorescence detection

Supervisors: Assoc Prof Todd A Houston, Dr Darren Grice, Assoc Prof Nick West (U.Queensland)

Medicinal Chemistry

Deadly infectious bacteria such as Mycobacterium tuberculosis and MRSA are able to survive within macrophages in a human host and this makes treatment particularly challenging. Incomplete or ineffective antibiotic treatment leads to development of drug resistant bacteria, a problem of growing global concern. We are currently developing antibacterial compounds that can be formulated into nanoparticles with drug targeting epitopes to improve uptake and drug delivery into macrophages. This allows for improved bactericidal activity and diminishes the opportunity for the development of drug resistance.

Techniques: Synthetic carbohydrate chemistry; liposome formulation; bacterial cell growth assays.

Supervisors: Assoc Prof Todd A Houston, Dr Michela Simone (U.Newcastle)

Medicinal Chemistry

Exo-glycosidases are an important family of enzymes involved in a number of vital biological process and pathologies. Glycosidase inhibitors have a wide range of medicinally-relevant activities including anti-cancer, anti-viral and anti-diabetic properties. Unfortunately, these compounds often have a relatively low affinity for their target enzyme.  We have identified an important structural motif that improves binding affinity of a number of glycosidase inhibitors, and this can be modified to improve drug targeting to cell surfaces where a number of enzyme targets are displayed.  In this way, the inhibitor can be placed in close proximity to the substrates the glycosidase enzyme

Techniques: Synthetic carbohydrate chemistry; molecular modelling; enzyme assays