Research areas
Research in the Butler Group is focussed on the design and synthesis of luminescent host molecules (or probes) for the selective recognition of biologically important substrates. These molecules are being developed into new tools for imaging, diagnostics and bioassay technologies. A fundamental goal of our research is to create supramolecular tools with real-world applications in biological and medical research. Research projects in the Butler group are multidisciplinary in nature; students receive training in a range of techniques in organic and peptide synthesis, molecular recognition, optical spectroscopy, bioassay development and cellular imaging.
Anion Receptors and Imaging Probes
We are developing luminescent anion receptors, based on designed lanthanide complexes, capable of binding and sensing nucleoside polyphosphate anions (e.g. ATP, ADP, GTP) in vitro and in living cells. Our synthetic receptors are able to monitor real-time changes in the concentrations of specific anions as they occur in enzymatic reactions, which could facilitate high-throughput screening of new potent enzyme inhibitors, a critical aspect of early stage drug discovery.
For example, we are developing molecules that can report on the phosphorylation of proteins, a process catalysed by kinase enzymes. Abnormal phosphorylation of proteins is the primary cause of many types of cancer. Synthetic receptors that can monitor protein phosphorylation are very well suited to screen for potential inhibitors or activators of kinase activity, and could facilitate the development of new therapeutic agents for the treatment of diseases such as cancer.
Macromolecular MRI Contrast Agents
We are developing new synthetic approaches to polymeric MRI contrast agents. MRI is an invaluable tool for imaging tumours and diagnosing disease. Commercial contrast agents have been used in the clinic since the 1980s, and are based on discrete Gd(III) complexes, which enhance the image contrast by increasing relaxation of local water molecules. However, these contrast agents are far from optimal, and the image contrast is nowhere near the theoretical maximum. We have designed monomeric Gd complexes bearing two polymerisable arms, which can be readily polymerised in a single step to form macromolecules with different architectures (e.g., hyperbranched polymers). By limiting the local motion of the Gd(III) complex through crosslinking of the monomer, we will deliver contrast agents with at least 7-fold higher relaxivities compared to commercial agents. This could enable lower, safer doses of the contrast agent to be used for MR imaging.
Key words
- Organic Synthesis
- Supramolecular Chemistry
- Luminescent Probes
- Cellular Imaging
- Lanthanide complexes
Research Opportunities
Enthusiastic postgraduate students and postdoctoral researchers are welcome to apply at any time to work in the areas of organic synthesis, ligand design and analysis of host-guest interactions. Fully funded positions will be advertised on the Group webpages when available. Researchers and students with their own funding are welcome to email Stephen directly.
