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 three million deaths per year (1 person every 7 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)

 

 

cover of Chem Med Chem Journalcover of chemical communications journal

 


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 Chem. Eur. J. 2012, 18(51), 16540-16548. DOI: 10.1002/chem.201202629; Angew. Chem. Int. Ed. 2011, 50, 1635-1639, DOI: 10.1002/anie.201006115; Chem. Commun. 2010, 46, 6249-6251. DOI: 10.1039/c0cc01360a)

 

 

cancer associated glycopeptide diagram

 

 


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)

 

Symplostatin 4 and Dolastatin-15 diagram

 


Project 4:

Nanoparticle therapeutics (with Professor Bob Prud'homme, Princeton University, USA)

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 and drug molecules. These functionalised nanoparticles will be used for the discovery of new inflammatory and HIV drug leads and cancer vaccine candidates. (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

Website: http://sydney.edu.au/science/chemistry/~payne