Diversity-oriented synthesis (DOS) is a modern chemical methodology, which aims to synthesise small molecules that cover new chemical space with the possibility of finding unexplored biological targets or pathways that may be important for disease progression. The development of novel chemical entities (NCEs) is very important to the field of chemical genetics where chemical probes are used to probe known or unknown biological targets.
This project will use DOS to enable the preparation of libraries of NCEs comprising heterocyclic pharmacophores, which will be used to probe the functional activity of enzyme targets. DOS will also be used to discover novel tool compounds including fluorescent molecules to probe regulation and functional activity of (i) aldehyde dehydrogenase (ALDH) isoforms highly expressed in cancer stem cells, (ii) cytochrome P450 (CYP) isoforms expressed in solid tumours or (iii) aldo-keto reductase 1C3 (AKR1C3) in prostate cancer. Conventional approaches such as computational modelling and medicinal chemistry will be employed in parallel to the use of DOS in order to develop chemical probes for enzyme interrogation.
We are looking for an enthusiastic student to develop effective chemical tool compounds that can be used for target interrogation in cell-free and cell-based assays. The student will be trained in the design of novel bioactive molecules including synthetic and computational studies as well as target interrogation in functional activity assays. Biological studies will include investigations comparing naked lead compounds with co-crystal versions to acquire knowledge essential for turning good chemical probes into potential drug candidates.
Applicants should have at least 2:1 honours degree in Chemistry, Chemical Biology, Pharmacy or related degree.