Industrial Research Ltd
Area/discipline of scienceSynthetic Organic Chemistry/Drug Discovery and Development/Anti-cancer and auto-immune disease
- Postdoctoral Research at the University of Oxford in asymmetric synthesis
- Ph.D. in Organic Chemistry from the University of Otago
- B.Sc. Hons I (Chemistry) from the University of Otago
As long as I can remember, chemistry has fascinated me. Chemistry brings about changes in matter and allows the synthesis of new chemical entities. Potentially, new chemical entities, synthesised by myself and other chemists throughout the world, promise a better life for all earth’s inhabitants, in the form of new materials, fuels and drugs, where used wisely and well. Excited by my empowerment through chemistry and the subsequent ability it gave me to create world-first, new chemical entities, I have spent the last 25 years as a bench chemist involved in drug discovery.
Chemistry now forms a seamless interface with biology and this critically affects drug discovery. Nearly one third of drugs marketed today work by blocking the action of enzymes. Enzymes are proteins essential for a large number of biological processes in all living organisms. The absence or over abundance of an enzyme can lead to disease within a living organism, such as a human being. Enzymes act as catalysts converting substrate(s) to product(s) via a high-energy intermediate known as a “transition state”. Enzymes enable this process by stabilising or lowering the energy of the transition state increasing the rate at which product(s) are formed by as much as a million million times. Stabilisation of the transition state occurs through additional bonds being formed to the substrate by the enzyme as it is shepherded through to the transition state.
Currently my research career involves the design and synthesis of chemical entities, which mimic the enzyme transition state, and encourage the formation, in situ, of the “stabilising bonds” and these entities have been coined “transition state analogues”. Synthesising or building a transition state analogue involves combining potentially hazardous chemicals in a controlled manner, identifying the structure of the product(s) via predominantly, nuclear magnetic resonance (NMR) and mass spectral analysis, and the repetition of this process to the point where the target is finally built. Building a transition state analogue can involve a lot of dead ends and frustrations. Transition state analogues are more active and infinitely more selective than traditional drugs.
These transition state analogues synthesised by my colleagues and myself have the potential to combat diseases such as cancer, malaria, and a variety of autoimmune diseases. To-date three putative drugs, which I first synthesised, have progressed through to pre-clinical and clinical trials and milestones like these continue to excite me. What doesn’t excite me is convincing the funding authorities of the worth of drug discovery being carried out in NZ, although, these necessary interactions do help “keep it real” and act as “a muse” inspiring my everyday creativity.