Kiefel Group

Supervisor: Assoc Prof Milton J Kiefel

Medicinal Chemistry

Ulosonic acids are a family of higher order sugars the are intimately associated with a number of human diseases.  Keto-deoxy octulosonic acids are key components of the outer membrane of Gram-negative bacteria, whilst nonulosonic acids include the sialic acids, pseudaminic acids, and legionaminic acids, all of which are known to be associated with human disease and bacterial virulence.  Whilst the role of these sugars as virulence factors is generally well understood, much remains to be discovered.  One of the current limitations in this field of research is the limited availability of synthetic derivatives and analogues of these important sugars.  This project aims to expand on some of our preliminary work into developing a new highly efficient synthesis of ulosonic acids using an aldol condensation as the key step.  Students undertaking this project will learn modern synthetic chemistry methodology in state-of-the-art chemistry research laboratories.  They will also gain "hands-on" experience with the use of high field NMR spectroscopy and will produce compounds that will ultimately be used as biological probes.

Supervisors: Assoc Prof Milton J. Kiefel & A/Prof Shai Anoopkumar-Dukie

Medicinal Chemistry

Butenolides are naturally occurring molecules characterised by a central 5-membered lactone ring.  There is vast structural diversity and biological activity within this group of naturally occurring compounds.  We have recently developed a highly efficient and flexible synthesis of this important class of natural products.  This project will focus on expanding our synthetic chemistry method to allow the synthesis of novel butenolides, and then evaluate the synthesised compounds for their biological activity.  Currently we have research looking at the anticancer activity of butenolides, but this can be expanded to include antimicrobial activity as well.

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 Milton J Kiefel, Professor Michael Jennings & Dr Freda  Jen

This project seeks to develop new methodologies to synthesise carbohydrates that can be used in a broader program that aims to develop a vaccine to protect against bacterial infection cause by non-typeable haemophilus influenzae and Neisseria gonorrhoeae.  The diseases caused by these bacteria are a major health and economic burden, and in the absence of new drugs a vaccine to prevent these diseases has emerged as a major unmet need in human health.