Dr Ivanhoe Leung
MChem, DPhil (Oxf)
I attained my undergraduate degree in Chemistry at the University of Oxford, as a member of St Peter’s College. I completed a DPhil in the laboratories of Profs Christopher J. Schofield FRS and Timothy D. W. Claridge, during which I applied NMR spectroscopy to study enzymes from an extended family of non-haem iron oxygenases that use 2-oxoglutarate as a cosubstrate. After my DPhil I spent a further two years in the same group as a postdoctoral research assistant, working on a variety of projects ranging from protein-ligand interactions, enzyme mechanisms, biocatalysis and enzyme inhibition. I also spent time as a visitor in the laboratory of Dr Isabelle Landrieu at the Université Lille 1, during which I utilised biomolecular NMR techniques to study protein dynamics. Since September 2014, I has been part of the University of Auckland and am currently a Senior Lecturer in Chemical Biology.
For more information about Ivan and his research team, please visit his Research Group Website.
Research | Current
The research of the Leung Group lies broadly at the interface between chemistry and biology with a focus on protein strcuture, function, mechanism and their links to the proteins’ biological roles. Our research is multidisciplinary, including chemistry, enzymology, molecular biology and biophysical methods. We collaborate closely with a number of research groups from the Schools of Chemical and Biological Sciences, as well as colleagues from overseas including the UK and Germany. Some examples of our current research areas include:
Protein-ligand interactions are fundamental to almost all biological processes in living organisms. These ligands range from small molecules to nucleic acids, peptides and proteins. We routinely apply biophysical techniques, including thermal shift assay, ITC, non-denaturing mass spectrometry and NMR spectroscopy, to screen for new protein ligands and quantify protein-ligand binding interactions. In addition, we also conduct method development work for the measurements of protein-ligand binding.
Example: Sci. Rep. 2017, 7, 43727.
Enzyme catalysis and inhibition
The understanding of enzyme catalysis and inhibition are critical to applications such as drug discovery and the development of agrochemicals. We apply biochemical and biophysical tools study enzyme kinetics and inhibition in order to understand the chemistry and mechanism of enzyme-catalysed reactions. We also apply protein NMR spectroscopy and X-ray crystallography to understand the structural bases of enzyme inhibitions.
Example: Bioorg. Med. Chem. Lett. 2017, 27, 277–281.
Posttranslational modification of proteins
Some proteins are known to undergo posttranslational modifications such as hydroxylation or phosphorylation. We apply biophysical and biochemical tools to visualise these modifications, and to study how posttranslational modification of proteins affect their structure, motion and function.
Example: Org. Biomol. Chem. 2017, 15, 1100–1105.
Teaching | Current
● CHEM 100 Molecules that Changed the World
● CHEM 260 Introduction to Green Chemistry
● CHEM 350 Topics in Chemistry
● CHEM 360 Contemporary Green Chemistry
● CHEM 390 Medicinal Chemistry
● CHEM 738 Biomolecular Chemistry (Course Coordinator)
● CHEM 750 Advanced Topics in Chemistry
● PHARMACY 211 Applied Science for Pharmacy
● PHARMACY 213 Pharmacy 1 (Guest Lecturer)
For more detailed information about potential research projects please contact Ivan via email. The work offers the opportunity to learn about research at the interface between chemistry and biology, and receive training in molecular biology, enzymology and NMR spectroscopy.
Journal Editorial Board
● Scientific Reports
● 2nd Asia Pacific Lysosomal Conference 2019, Scientific Committee
● Green Chemistry New Zealand 2017, Organising Committee (Co-Chair)
● New Zealand Institute of Chemistry (NZIC) Auckland Branch, Treasurer
● The New Zealand Society for Biochemistry and Molecular Biology (NZSBMB), Auckland Representative
The University of Auckland
● SCS Health and Safety Committee, Chair
● Centre for Green Chemical Science, Co-Deputy Director
● School Executive Committee, Member
● CGPM Mass Spectrometry Academic Steering Group, Member
● NMR Management Group, Member
Areas of expertise
● Biological and organic NMR spectroscopy
● Biophysical techniques to study enzyme kinetics and protein-ligand interactions
● Ligand screening and inhibitor discovery
● Mechanistic enzymology
● Protein chemistry
● Protein-directed dynamic combinatorial chemistry
Selected publications and creative works (Research Outputs)
- Zakharenko, A. L., Luzina, O. A., Sokolov, D. N., Kaledin, V. I., Nikolin, V. P., Popova, N. A., ... Zafar, A. (2019). Novel tyrosyl-DNA phosphodiesterase 1 inhibitors enhance the therapeutic impact of topoteсan on in vivo tumor models. European journal of medicinal chemistry, 161, 581-593. 10.1016/j.ejmech.2018.10.055
Other University of Auckland co-authors: Johannes Reynisson, Euphemia Leung, Jinal Patel
- Huang, R., & Leung, I. K. H. (2019). Protein-Small Molecule Interactions by WaterLOGSY. (pp. 477-500). 10.1016/bs.mie.2018.08.020
- Xiang, L., Melton, L. D., & Leung, I. K. H. (2019). Interactions of β-Lactoglobulin With Small Molecules. In P. Varelis, L. Melton, F. Shahidi (Eds.) Encyclopedia of Food Chemistry (pp. 560-565). Elsevier. 10.1016/B978-0-08-100596-5.21488-1
- Son, S. J., Huang, R., Squire, C. J., & Leung, I. K. H. (2019). MCR-1: a promising target for structure-based design of inhibitors to tackle polymyxin resistance. Drug discovery today, 24 (1), 206-216. 10.1016/j.drudis.2018.07.004
Other University of Auckland co-authors: Renjie Huang, Christopher Squire
- Abboud, M. I., Chowdhury, R., Leung, I. K. H., Lippl, K., Loenarz, C., Claridge, T. D. W., & Schofield, C. J. (2018). Studies on the Substrate Selectivity of the Hypoxia-Inducible Factor Prolyl Hydroxylase 2 Catalytic Domain. Chembiochem : a European journal of chemical biology, 19 (21), 2262-2267. 10.1002/cbic.201800246
- Li-Zhulanov, N. S., Zakharenko, A. L., Chepanova, A. A., Patel, J., Zafar, A., Volcho, K. P., ... Lavrik, O. I. (2018). A Novel Class of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Contains the Octahydro-2H-chromen-4-ol Scaffold. Molecules (Basel, Switzerland), 23 (10).10.3390/molecules23102468
Other University of Auckland co-authors: Ayesha Zafar, Johannes Reynisson, Jinal Patel
- Zhang, S., De Leon Rodriguez, L. M., Huang, R., Leung, I. K. H., Harris, P. W. R., & Brimble, M. A. (2018). Total synthesis of the proposed structure of talarolide A. Organic & biomolecular chemistry, 16 (29), 5286-5293. 10.1039/c8ob01230j
Other University of Auckland co-authors: Margaret Brimble, Paul Harris, Renjie Huang
- McAllister, T. E., Yeh, T.-L., Abboud, M. I., Leung, I. K. H., Hookway, E. S., King, O. N. F., ... Münzel M (2018). Non-competitive cyclic peptides for targeting enzyme-substrate complexes. Chemical science, 9 (20), 4569-4578. 10.1039/c8sc00286j