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Dr Peter J Rutledge


Contact Details

Senior Lecturer
Room 547
School of Chemistry, Building F11
The University of Sydney, NSW, 2006, Australia
E: peter.rutledge@sydney.edu.au
T: +61 (2) 9351 5020
F: +61 (2) 9351 3329
W: http://sydney.edu.au/science/chemistry/~rutledge/

Career Profile

  • BSc & MSc (Hons I) The University of Auckland, New Zealand. (1991-1995)
  • DPhil The Dyson Perrins Laboratory & Magdalen College, Oxford, UK. (1995-1999)
  • Postdoctoral Research Fellow, The Dyson Perrins Laboratory, Oxford. (1999-2002)
  • Lecturer, Magdalen & Somerville Colleges, Oxford. (2000-2002)
  • Lecturer, Centre for Synthesis & Chemical Biology, University College Dublin. (2003-2006)
  • Lecturer, School of Chemistry, The University of Sydney (2006-2008)
  • Senior lecturer, School of Chemistry, The University of Sydney (2009 - )
  • Visiting Fellow, The University of Warwick (2012)

Recent Achievements

  • 2012: Pearson Education RACI Centenary of Federation Chemistry Educator of the Year Award
  • 2011: Vice-Chancellor's Award for Outstanding Teaching
  • 2010: Vice-Chancellor's Award for Support of the Student Experience
  • 2009: RACI NSW President’s Citation
  • 2008: NSW and ACT Young Tall Poppy Science Award
  • 2007: RACI Athel Beckwith Lectureship
  • 2006: RACI Nyholm Lectureship

Details of Research

Hydrocarbon Oxidation and C–H Activation:

The conversion of simple hydrocarbons (alkanes, alkenes and aromatic compounds) to functionalised targets is of great interest in synthetic and medicinal chemistry, but many of these key transformations are inaccessible with current synthetic methods. Nature uses highly efficient enzyme systems to oxidise hydrocarbons in high yield with complete selectivity. We are working to develop new catalysts inspired by these biological systems, and to use them for the selective oxidation of hydrocarbon substrates: new reagents for synthesis and for the environment. We have synthesised a series of small-molecule systems that mimic the non-heme iron oxidase (NHIO) active site and are developing these as catalysts for biomimetic hydrocarbon oxidation and iron-mediated C–H activation.

Antibiotics Chemistry:

The rise and rise of the so-called ‘Superbugs’ is well documented in the media. Bacteria that are resistant to (i.e. not killed by) most current antibiotics are increasingly widespread, and the need for new drugs and new strategies to combat them grows ever more important. We are widely interested in antibiotics chemistry and antibiotic biosynthesis, and are pursuing a number of approaches to meet the challenges posed by antibiotic resistant bacteria. Current strategies include the synthesis of new cyclobutanone antibiotics and the design of antibiotics with novel ‘double-punch’ and ‘resistance-activated’ modes of action.

Mercury Binding:

Heavy metals like cadmium and mercury form some of the most toxic materials known. Yet some plants and microbes have developed strategies to live in locales prone to high levels of cadmium and mercury pollution, using sulfur-rich proteins to bind and the toxic metal ions and sequester them away from the rest of the cell’s machinery. These proteins incorporate high numbers of cysteine residues, which makes them effective agents for heavy metal sequestration: the numerous sulfur atoms bind tightly to mercury, cadmium and other metal ions. Our approach uses thiol- and sulfide-rich peptides as agents for binding and sensing mercury.

Nitrile Hydratase Mimics and Mechanism:

Nitrile hydratase is an unusual metalloenzyme that brings about the selective conversion of nitriles to primary amides. Crystal structures of nitrile hydratases show a remarkable ligand environment in the active site. Two nitrogen atoms from main-chain amides bind to the metal (iron(III) or cobalt(III)), along with three sulfur atoms, each in a different oxidation state. And these five metal binding ligands are located in a short section of the primary sequence, spread across only six amino acids in one peptide chain. We are working to develop new peptide-based systems as bio-inspired catalysts for nitrile hydration, to study the unusual sulfur oxidation that occurs at the nitrile hydratase active site, and to elucidate a detailed mechanism for nitrile hydratase catalysis.

For further details on all of these areas, please see the Rutledge Group Research page

Publications (2009 to 2013)

  1. Daruzzaman, A; Clifton, IJ; Adlington, RM; Baldwin, JE and Rutledge, PJ. The interaction of isopenicillin N synthase with homologated substrate analogues δ-(L-α-aminoadipoyl)-L-homocysteinyl-D-Xaa characterised by protein crystallography. ChemBioChem, 14 (5), 599-606, 2013. DOI: 10.1002/cbic.201200728

  2. Cheung, S; McCarl, V; Holmes, AJ; Coleman, NV and Rutledge, P. Substrate range and enantioselectivity of epoxidation reactions mediated by the ethene-oxidising Mycobacterium strain NBB4. Applied Microbiological Biotechnology, 97 (3), 1131-1140, 2013. DOI: 10.1007/s00253-012-3975-6

  3. Dungan, VJ; Poon, BM-L; Barrett, ES and Rutledge, PJ. L-Proline derived mimics of the non-haem iron active site catalyse allylic oxidation in acetonitrile solutions. Tetrahedron Letters, 54 (10), 1236-1238, 2013. DOI: 10.1016/j.tetlet.2012.12.095

  4. Daruzzaman, A; Clifton, IJ; Adlington, RM; Baldwin, JE and Rutledge, PJ. The crystal structure of isopenicillin N synthase with a dipeptide substrate analogue. Archives of Biochemistry and Biophysics, 530 (1), 48-53, 2013. DOI: 10.1016/j.abb.2012.12.012

  5. Yu, M; Yu, Q; Rutledge, PJ and Todd, MH. A fluorescent "allosteric scorpionand" complex visualizes a biological recognition event. ChemBioChem, 14 (2), 224-229, 2013. DOI: 10.1002/cbic.201200637

  6. Ast, S; Rutledge, PJ and Todd, MH. Reversing the triazole topology in a cyclam-triazole-dye ligand gives a 10-fold brighter signal response to Zn2+ in aqueous solution. European Journal of Inorganic Chemistry, (34), 5611-5615, 2012. DOI: 10.1002/ejic.201201072

  7. Dungan, VJ; Mueller-Bunz, H and Rutledge, RJ. (2S,4S)-3-benzoyl-4-benzyl-2-tert-butyl-1,3-oxazolidin-5-one. Acta Crystallographica Section E, E68 (9), o2747-o2755, 2012. DOI: 10.1107/S1600536812035556

  8. Barry, SM; Mueller-Bunz, H and Rutledge, PJ. Investigating the oxidation of alkenes by non-heme iron enzyme mimics. Organic & Biomolecular Chemistry, 10 (36), 7372-7381, 2012. DOI: 10.1039/c2ob25834j

  9. Beare, KD; Coster, MJ and Rutledge, PJ. Diketoacid inhibitors of HIV-1 integrase: From L-708,906 to raltegravir and beyond. Current Medicinal Chemistry, 19 (8), 1177-1192, 2012. DOI: 10.2174/092986712799320565

  10. Dungan, VJ; Wong, SM; Barry, SM and Rutledge, PJ. L-proline-derived ligands to mimic the '2-His-1-carboxylate' triad of the non-haem iron oxidase active site. Tetrahedron, 68 (15), 3231-3236, 2012. DOI: 10.1016/j.tet.2012.02.031

  11. Yu, M; Price, JR; Jensen, P; Lovitt, CJ; Shelper, T; Duffy, S; Windus, LC; Avery, VM; Rutledge, PJ and Todd, MH. Copper, nickel, and zinc cyclam-amino acid and cyclam-peptide complexes may be synthesized with “click” chemistry and are noncytotoxic. Inorganic Chemistry, 50 (24), 12823-12835, 2011. DOI: 10.1021/ic2020012

  12. Clifton, IJ; Ge, W; Adlington, RM; Baldwin, JE and Rutledge, PJ. The crystal structure of isopenicillin N synthase with delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-methionine reveals thioether coordination to iron. Archives of Biochemistry and Biophysics, 516 (2), 103-107, 2011. DOI: 10.1016/j.abb.2011.09.014

  13. Clifton, IJ; Ge, W; Adlington, RM; Baldwin, JE and Rutledge, PJ. Isopenicillin N synthase binds delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-thia-allo-isoleucine through both sulfur atoms. ChemBiochem, 12 (12), 1881-1885, 2011. DOI: 10.1002/cbic.201100149

  14. Lo, ATS; Salam, NK; Hibbs, DE; Rutledge, PJ and Todd, MH. Polyamide-scorpion cyclam lexitropsins selectively bind AT-rich DNA independently of the nature of the coordinated metal. PLoS one, 6 (5), e17446, 2011. DOI: 10.1371/journal.pone.0017446

  15. Lau, YH; Rutledge, PJ; Watkinson, M and Todd, MH. Chemical sensors that incorporate click-derived triazoles. Chemical Society Reviews, 40 (5), 2848-2866, 2011.DOI: 10.1039/c0cs00143k

  16. Bridgeman, AJ; Rutledge, PJ; Todd, MH and Connor, R. A treasure hunt for chemistry. Journal of Chemical Education, 88 (4), 437-439, 2011. DOI: 10.1021/ed100867m

  17. Lau, YH; Price, JR; Todd, MH and Rutledge, PJ. A click fluorophore sensor that can distinguish CuII and HgII via selective anion-induced demetallation. Chemistry: A European Journal, 17 (10), 2850-2858, 2011. DOI: 10.1002/chem.201002477

  18. Scully, CCG; Lau, YH; Jensen, P and Rutledge, PJ. Synthesis, electrochemistry and metal binding properties of monosubstituted ferrocenoyl peptides with thioether-containing sidechains. Journal of Organometallic Chemistry, 696 (3), 715-721, 2011. DOI: 10.1016/j.jorganchem.2010.09.056

  19. Hosseini, SS; Bhadbhade, M; Clarke, RJ; Rutledge, PJ and Rendina, LM. Synthesis, carbohydrate- and DNA-binding studies of cationic 2,2':6',2"-terpyridineplatinum(II) complexes containing N- and S-donor boronic acid ligands. Dalton Transactions, 40 (2), 506-513, 2011. DOI: 10.1039/c0dt00892c

  20. Morrison, DE; Issa, F; Bhadbhade, M; Groebler, L; Witting, PK; Kassiou, M; Rutledge, PJ and Rendina, LM. Boronated phosphonium salts containing arylboronic acid, closo-carborane, or nido-carborane: Synthesis, X-ray diffraction, in vitro cytotoxicity, and cellular uptake. J. Biol. Inorg. Chem., 15 (8), 1305-1318, 2010.DOI: 10.1007/s00775-010-0690-6

  21. Ge, W; Clifton, IJ; Stok, JE; Adlington, RM; Baldwin, JE and Rutledge, PJ. Crystallographic studies on the binding of selectively deuterated LLD- and LLL-substrate epimers by isopenicillin N synthase. Biochemical and Biophysical Research Communications, 398 (4), 659-664, 2010. DOI: 10.1016/j.bbrc.2010.06.129

  22. Scully, CCG and Rutledge, RJ. Synthesis and electrochemical studies of disubstituted ferrocene/dipeptide conjugates with sulfur-containing side chains. Tetrahedron, 66 (30), 5653-5659, 2010. DOI: 10.1016/j.tet.2010.05.070

  23. Manos-Turvey, A; Bulloch, EMM; Rutledge, PJ; Baker, EN; Lott, JS and Payne, RJ. Inhibition studies of Mycobacterium tuberculosis salicylate synthase (Mbtl). ChemMedChem, 5 (7), 1067-1079, 2010. DOI: 10.1002/cmdc.201000137

  24. Dungan, VJ; Ortin, Y; Mueller-Bunz, H and Rutledge, PJ. Design and synthesis of a tetradentate ‘3-amine-1-carboxylate’ ligand to mimic the metal binding environment at the non-heme iron(II) oxidase active stie. Org. Biomol. Chem., 8 (7), 1666-1673, 2010. DOI: 10.1039/b921934j

  25. Ge, W; Clifton, IJ; Stok, JE; Adlington, RM; Baldwin, JE and Rutledge, PJ. The crystal structure of an LLL-configured depsipeptide substrate analogue bound to isopenicillin N synthase. Org. Biomol. Chem., 8 (1), 122-127, 2010. DOI: 10.1039/b910170e

  26. Ge, W; Clifton, IJ; Howard-Jones, AR; Stok, JE; Adlington, RM; Baldwin, JE and Rutledge, PJ. Structural studies on the reaction of isopenicillin N synthase with a sterically demanding depsipeptide substrate analogue. ChemBioChem, 10 (12), 2025-2031, 2009. DOI: 10.1002/cbic.200900080