We are a medicinal and synthetic chemistry lab developing novel synthetic chemistry to design and synthesise bio-active small molecules. Along with our network of collaborators, we test these compounds against a wide variety of targets and disease states to aid in the discovery of new therapeutics.
We are actively designing and synthesising small molecules to interact with a range of biological targets. Our group uses both structure based and fragment based drug discovery techniques to help in our designs. Below are several projects currently underway.
Targeting the Untargeted Kinome
It is well known that kinases have become one of the most important biological targets within drug discovery arena, with successes stemming from the initial FDA approval of Imatinib for chronic myeloid leukaemia. Although kinases have been extensively studied, the majority of research carried out on kinases only surveys a small percentage of the known kinome. This has resulted in a very skewed distribution of knowledge about their biological function. Our lab works to address this imbalance, and we have identified several important families to target. In particular we are focussing our efforts on cyclin-dependent kinases, pseudokinases, and histidine kinases, using small molecules to probe their biological function
Combating Rare Disease
It is an unfortunate fact that many global pharmaceutical companies are no longer developing drugs for rare disease. Our lab, in collaboration with both structural biologists and clinical biochemists, is working to benefit patients who are living with these often debilitating conditions. We use cutting edge screening platforms to identify chemical leads, which will be optimised for potency, selectivity and cellular activity. These small molecules will then be evaluated as a potential therapeutic by our network of collaborators. Our initial efforts are focussed on developing a substrate reduction therapy for a rare form of childhood epilepsy called pyridoxine dependent epilepsy or PDE.
There is currently an unmet need for new antibiotics targeting a range of bacteria. Along with colleagues in the Department of Life Sciences, we are actively designing small molecules to inhibit a several unexplored targets within bacteria. In particular, we are working towards small molecules that have greater activity against MRSA, with a much improved toxicity profile.
New Modalities for the Treatment of Cardiovascular Disease
CVD is a leading cause of mortality worldwide, and a major area of concern for health systems globally. Our collaborative work is looking at ways to reduce the prevalence of this disease through modulation of platelet behavior. Using cutting edge structural, chemical and cell biology, and pairing this with in house developed synthetic chemistry, we are progressing a range of small molecule probes to assess the importance of several key targets.
Synthetic Organic Chemistry
The group is also interested in developing new and useful synthetic transformations and using these to help us synthesise novel small molecules.
Alkaline earth metal catalysis
We are interested in using Group 2 metals as catalysts to power organic reactions, and in particular using calcium as a highly sustainable, redox neutral and environmentally benign metal catalyst. We are using calcium to control a range of useful reactions as shown below.
We are interested in developing novel, superacid catalysed transformations which lead to important structural motifs. In particular, we are pursuing several key projects looking at acids with differential electronics and pairing these with chiral ligands
Enantioselective Cross Coupling Reactions
The need to develop new methods to couple two, racemic partners together remain as important as ever. Our group aims to establish novel cross-coupling protocols to join traditionally inert coupling partners together in a stereoselective manner. Taking advantage of the numerous chiral ligands available, we aim to develop more robust and user friendly approaches to deliver stereoenriched compounds.