organic synthesis, drug discovery and chemical biology
Research in my group is focussed on utilising synthetic organic chemistry to address problems of medical significance. There is a wide range of projects available; the choice is not restricted to those shown here and more information can be provided.
Project 1
Tuberculosis and malaria drug discovery
Tuberculosis (TB) and malaria represent two of the most deadly infectious diseases, responsible for approximately four million deaths per year (1 person every 5 seconds). New drugs are desperately needed for these diseases due to the rapid emergence of drug resistance. Several projects are available which use a combination of synthetic organic chemistry, computer-aided drug discovery and drug screening technologies to develop novel small molecule inhibitors against validated target enzymes essential for the growth of the bacterium (in TB) and the parasite (in malaria). These compounds will serve as TB and malarial drug leads (see ChemMedChem, 2012, 7, 1031-1043, DOI: 10.1002/cmdc.201100606; Chem. Commun., 2011, 47, 5166-5168, DOI: 10.1039/c0cc05635a; ChemMedChem, 2010, 5, 1067-1079. DOI: 10.1002/cmdc.201000137
Project 2
Synthesis of glycopeptide-based cancer vaccines
In cancer cells there is a significant increase in the expression of a number of glycoproteins. This makes a cancer cell look different to a normal cell and opens up avenues for the development of glycopeptide-based cancer vaccines. This project will use solid-phase peptide synthesis and organic synthesis to produce defined glycopeptide segments of cancer-associated cell-surface glycoproteins. These will be covalently linked to immune-stimulating molecules to elicit a favourable immune response (see vaccine structure below). These molecules include a foreign peptide to stimulate T-cells (a T-cell helper epitope) and an immunoadjuvant (a lipopeptide which stimulates pattern recognition receptors on human cells). The compounds synthesised in this project will be used to generate tumour-selective antibodies in immunological studies thus allowing for their evaluation as anti-cancer vaccines (see Angew. Chem. Int. Ed. 2011, 50, 1635-1639, DOI: 10.1002/anie.201006115; Chem. Commun. 2010, 46, 6249-6251. DOI: 10.1039/c0cc01360a
Project 3
Total synthesis of marine natural projects as anti-cancer drug leads
Symplostatin-4 and the Dolastatins are natural products isolated from marine cyanobacteria (pictured below). As a result of their potent cytotoxic activity, compounds based on these natural products have recently entered phase II clinical trials as new anti-cancer drugs. This project will involve the total synthesis of hybrid analogues of these compounds. The project will involve a combination of solution- and solid-phase organic synthesis as well as compound screening to gauge their anti-cancer activity. (see Chem. Eur. J., 2011, 17, 13544-13552, DOI: 10.1002/chem.201102538; Org. Lett., 2011, 12, 5576-5579, DOI: 10.1021/ol1024663
Project 4:
Nanoparticle therapeutics
Nanoparticles that possess a multivalent display of biomolecules on their surface (including DNA, peptides and carbohydrates) have emerged as promising cellular mimics for the study of biological processes and for the discovery of novel therapeutics. In this project you will synthesise and decorate polymeric nanoparticles with a range of biomolecules, which will be used in the discovery of new inflammatory and HIV drug leads and cancer vaccine candidates. The biomolecules will include carbohydrates, peptides and glycopeptides, which will be synthesised by a combination of cutting edge solution and solid-phase synthetic methods. (see Chem Commun., 2010, 46, 2188-2190. DOI: 10.1039/b924112d
For further information, please contact:
Associate Professor Richard Payne
Room 545
School of Chemistry
Eastern Avenue
University of Sydney NSW 2006
Phone: +61 2 9351 5877
Email: richard.payne@sydney.edu.au