synthesis, sensing and chemical biology



Research in the Rutledge group uses the tools of organic synthesis and bio-organic chemistry to develop new antibiotics and cancer drugs, create biologically-inspired catalysts for important synthetic transformations, and design chemical solutions to environmental problems.

 

Fluorescent dye for use in metal ion sensors. Photo courtesy of Cyril Tang.

Fluorescent dye for use in metal ion sensors. Photo courtesy of Cyril Tang.


Project 1

Metal ion sensors for biology, medicine and the environment

Metal cations like Zn(II), Cu(II) and K(I) play a range of important signalling roles in the body. We are developing fluorescent sensors to image these metal ions inside and just outside cells as new tools for diagnosing diseases like diabetes, cancer and Alzheimer’s disease. We have recently reported a zinc sensor with ten-fold a brighter signal response to zinc(II) (1, see Eur. J. Inorg. Chem. 2012 5611 (2012)) and a copper sensor that functions selectively in doped aqueous saline solutions (2, see Chem. Eur. J. 17 2850 (2011)). Now we are working to:

  1. develop new systems with improved fluorescence properties;
  2. increase the responsiveness of our sensors by incorporating fluorescent nanoparticles (quantum dots (QDs), with Dr Mat Todd);
  3. enhance sensitivity by attaching them to optical fibres (collaboration with Professor John Canning).

In a parallel approach we are applying a similar strategy to develop new sensors for heavy metal pollutants such as mercury, cadmium and lead, for environmental applications (see Chem. Eur. J. 17 2850 (2011) or J. Organomet. Chem. 696 715 (2011)).
Working on this project you will develop skills in organic synthesis, spectroscopy, chromatography, coordination chemistry and fluorescence techniques, plus either nanotechnology (QDs) or photonics (optical fibres).

 

 

Naphthalimide diagram

 


Project 2

Fluorescent imaging agents for cancer diagnostics

Building on our work with fluorescent metal sensors (see Project 1) we are building a new kind of imaging agent for biomolecules that are overexpressed in cancer cells. These compounds change their behaviour in the presence of their biomolecular target so are activated only when they bind that target (see ChemBioChem 14 224 (2013) and Chem. Open 2 99 (2013)). We are developing responsive imaging agents to be activated by specific interactions with targets associated with cancer cells (eg matrix metalloproteinases; estrogen receptors), to build new cancer detection technologies and anti-cancer agents. Working on this project you will use organic synthesis, spectroscopy (including 1H and 13C NMR, IR, mass spectrometry), coordination chemistry and fluorescence techniques, and to collaborate with the groups of Dr Mat Todd and Associate Professor Jamie Triccas (Sydney Medical School).

 


Project 3

Antibiotics chemistry

Bacterial resistance to antibiotics is an ever more urgent challenge for modern science and medicine. We are developing new ways to combat resistant bacteria:

  • ‘double-punch’ and ‘resistance-activated’ antibiotics;
  • cyclobutenone analogues 3 of traditional β-lactams 4 (see ChemBioChem 8 2003 (2007)) as β-lactamase inhibitors (figure shows a cyclobutanone β-lactam analogue covalently bound to serine β-lactamase as a hemiketal, from the work of Dmetrienko et al. J. Am. Chem. Soc. 132 2558 (2010));
  • new antimycobacterial agents with unprecedented structures and high potency against Mycobacterium tuberculosis and M. avium (collaboration with Dr Mat Todd and Associate Professor Jamie Triccas).

Working on this project you will develop skills in organic synthesis, spectroscopy, chromatography and coordination chemistry, and have the opportunity to conduct biological assays on the compounds you make in association with our collaborators in the Sydney Medical School.

 

 


Project 4

Biocatalysis and bio-inspired catalysis

The development of efficient methods to selectively functionalise C–H bonds (ie convert C–H bonds to C–O or C–N bonds) is an area of great interest in organic chemistry. Iron has great potential in this area due to its availability, affordability and ability to promote a range of oxidation reactions. We have recently reported a new biocatalytic system that converts simple alkenes 5 to chiral epoxides 6 (see Appl. Microbiol. Biotechnol. 97 1131 (2013)), and a range of ‘bio-inspired’ iron-based catalysts that oxidise hydrocarbon substrates (see for example Tetrahedron Lett. 54 1236 (2013) or Org. Biomol. Chem. 10 7372 (2012)). Two project areas are offered in 2014:

  1. biocatalysis – developing the potential of our new biocatalyst for alkene epoxidation using directed evolution and gene knock-out strategies (collaboration with Dr Nick Coleman, School of Molecular Biosciences);
  2. bio-inspired catalysis – creating new bio-inspired catalysts for allylic amination reactions, nitrile hydration, DNA cleavage and peptide hydrolysis.

 

 

Working on this project, you will use peptide synthesis and a range of spectroscopic methods to characterise the new systems, including 1H and 13C NMR and IR, mass spectroscopy, EPR, XAFS and gas chromatography. You will also have the opportunity to develop skills in biocatalysis, microbiology and molecular biology in collaboration with the Coleman group.

 

(from Chem. Eur. J. 17 2850 (2011))

 

 


For further information, please contact:

Associate Professor Peter Rutledge

Room 547

School of Chemistry

Eastern Avenue

University of Sydney NSW 2006

Phone: +61 2 9351 5020

Email: peter.rutledge@sydney.edu.au

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